Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Review Article

Targeting Neuroinflammation as Disease Modifying Approach to Alzheimer’s Disease: Potential and Challenges

Author(s): Smita Jain, Ritu Singh, Sarvesh Paliwal and Swapnil Sharma*

Volume 23, Issue 22, 2023

Published on: 12 June, 2023

Page: [2097 - 2116] Pages: 20

DOI: 10.2174/1389557523666230511122435

Price: $65

Abstract

Alzheimer's disease (AD) is the most common form of dementia, having characteristic clinical features of progressive memory loss and visuospatial, language, and cognitive impairment. In addition, patients often suffer from comorbid depression and aggression. Aging is a major contributing factor, though the exact pathophysiological involvement in the disease progression is debatable. Biologists demonstrate that AD is not a result of a single pathological incident. However, an uncontrolled myriad of events is responsible for the pathophysiological condition; hence, it is regarded as a multifaceted disease. Pathophysiologically, AD is described by having a long preclinical stage (proteinopathy accumulation stage), followed by a short prodromal/dementia stage (clinical symptom onset), as evident via biomarker studies. Specific and sensitive biomarkers are needed to track disease progression and treatment. Neuroinflammation is one of the cardinal pathophysiological events of AD that form a positive activation loop between proteinopathy and pro-inflammatory mediators. However, the starting point is inconclusive. The vital cells, like glia, known as brain scavenger cells, remain in harmony between their quiescent and activated morphological states during any stimulus and help to regulate the neuroinflammatory microenvironment. Hence, focusing on the dysfunctional microglia could be a novel therapeutic approach to managing neuroinflammation condition in AD. This review focuses on the translational evidence of anti-diabetic and anti-inflammatory candidates in AD management. It also highlights the importance of the microglia activation spectrum, eicosanoid signaling, cytokine signaling, and inflammatory mediators responsible for the neuroinflammation cascade. The repeated failure of single-approached therapies has diverted researchers’ attention to AD-modifying approaches and AD multimodal treatment plans. This review is an effort to brief the role of new players (like micronutrients and nutraceutical applications) that have been reported as helpful in suppressing AD severity. Apart from anti-diabetic candidates, various insulin-mimetic and insulin-sensitizer drugs have also been assessed to target insulin insensitivity to mitigate AD progression. However, these possibilities are in the investigational stage and not clinically established yet, though various AD animal models have verified the positive outcome.

Graphical Abstract

[1]
Jain, S.; Bisht, A.; Verma, K.; Negi, S.; Paliwal, S.; Sharma, S. The role of fatty acid amide hydrolase enzyme inhibitors in Alzheimer’s Disease. Cell Biochem. Funct., 2021, 40, 106-117.
[http://dx.doi.org/10.1002/cbf.3680] [PMID: 34931308]
[2]
Rubio-Perez, J.M.; Morillas-Ruiz, J.M. A review: Inflammatory process in Alzheimer’s disease, role of cytokines. Sci. World J., 2012, 2012, 1-15.
[http://dx.doi.org/10.1100/2012/756357] [PMID: 22566778]
[3]
Askin, S.; Tahtaci, H. Türkeş C.; Demir, Y.; Ece, A.; Akalın Çiftçi, G.; Beydemir, Ş. Design, synthesis, characterization, in vitro and in silico evaluation of novel imidazo[2,1-b][1,3,4]thiadiazoles as highly potent acetylcholinesterase and non-classical carbonic anhydrase inhibitors. Bioorg. Chem., 2021, 113, 105009.
[http://dx.doi.org/10.1016/j.bioorg.2021.105009] [PMID: 34052739]
[4]
Knopman, D.S.; Amieva, H.; Petersen, R.C.; Chételat, G.; Holtzman, D.M.; Hyman, B.T.; Nixon, R.A.; Jones, D.T. Alzheimer Disease. Nat. Rev. Dis. Primers, 2021, 7(1), 1-21.
[http://dx.doi.org/10.1038/s41572-021-00269-y]
[5]
Alzheimer’s Disease. Facts Fig; Alzheimer’s Association, 2022.
[6]
Türkan, F.; Huyut, Z.; Demir, Y. Ertaş F.; Beydemir, Ş. The effects of some cephalosporins on acetylcholinesterase and glutathione S-transferase: an in vivo and in vitro study. Arch. Physiol. Biochem., 2019, 125(3), 235-243.
[http://dx.doi.org/10.1080/13813455.2018.1452037] [PMID: 29564935]
[7]
Gümüş M.; Babacan, Ş.N.; Demir, Y.; Sert, Y.; Koca, İ.; Gülçin, İ. Discovery of sulfadrug–pyrrole conjugates as carbonic anhydrase and acetylcholinesterase inhibitors. Arch. Pharm., 2022, 355(1), 2100242.
[http://dx.doi.org/10.1002/ardp.202100242] [PMID: 34609760]
[8]
Calsolaro, V.; Edison, P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement., 2016, 12(6), 719-732.
[http://dx.doi.org/10.1016/j.jalz.2016.02.010] [PMID: 27179961]
[9]
Szabo, L.; Eckert, A.; Grimm, A. Insights into disease-associated tau impact on mitochondria. Int. J. Mol. Sci., 2020, 21(17), 6344.
[http://dx.doi.org/10.3390/ijms21176344] [PMID: 32882957]
[10]
Vogel, J.W.; Iturria-Medina, Y.; Strandberg, O.T.; Smith, R.; Levitis, E.; Evans, A.C.; Hansson, O.; Weiner, M.; Aisen, P.; Petersen, R.; Jack, C.R., Jr; Jagust, W.; Trojanowki, J.Q.; Toga, A.W.; Beckett, L.; Green, R.C.; Saykin, A.J.; Morris, J.; Shaw, L.M.; Liu, E.; Montine, T.; Thomas, R.G.; Donohue, M.; Walter, S.; Gessert, D.; Sather, T.; Jiminez, G.; Harvey, D.; Donohue, M.; Bernstein, M.; Fox, N.; Thompson, P.; Schuff, N. DeCArli, C.; Borowski, B.; Gunter, J.; Senjem, M.; Vemuri, P.; Jones, D.; Kantarci, K.; Ward, C.; Koeppe, R.A.; Foster, N.; Reiman, E.M.; Chen, K.; Mathis, C.; Landau, S.; Cairns, N.J.; Householder, E.; Reinwald, L.T.; Lee, V.; Korecka, M.; Figurski, M.; Crawford, K.; Neu, S.; Foroud, T.M.; Potkin, S.; Shen, L.; Kelley, F.; Kim, S.; Nho, K.; Kachaturian, Z.; Frank, R.; Snyder, P.J.; Molchan, S.; Kaye, J.; Quinn, J.; Lind, B.; Carter, R.; Dolen, S.; Schneider, L.S.; Pawluczyk, S.; Beccera, M.; Teodoro, L.; Spann, B.M.; Brewer, J.; Vanderswag, H.; Fleisher, A.; Heidebrink, J.L.; Lord, J.L.; Petersen, R.; Mason, S.S.; Albers, C.S.; Knopman, D.; Johnson, K.; Doody, R.S.; Meyer, J.V.; Chowdhury, M.; Rountree, S.; Dang, M.; Stern, Y.; Honig, L.S.; Bell, K.L.; Ances, B.; Morris, J.C.; Carroll, M.; Leon, S.; Householder, E.; Mintun, M.A.; Schneider, S.; OliverNG, A.; Griffith, R.; Clark, D.; Geldmacher, D.; Brockington, J.; Roberson, E.; Grossman, H.; Mitsis, E.; de Toledo-Morrell, L.; Shah, R.C.; Duara, R.; Varon, D.; Greig, M.T.; Roberts, P.; Albert, M.; Onyike, C.; D’Agostino, D., II; Kielb, S.; Galvin, J.E.; Pogorelec, D.M.; Cerbone, B.; Michel, C.A.; Rusinek, H.; de Leon, M.J.; Glodzik, L.; De Santi, S.; Doraiswamy, P.M.; Petrella, J.R.; Wong, T.Z.; Arnold, S.E.; Karlawish, J.H.; Wolk, D.; Smith, C.D.; Jicha, G.; Hardy, P.; Sinha, P.; Oates, E.; Conrad, G.; Lopez, O.L.; Oakley, M.A.; Simpson, D.M.; Porsteinsson, A.P.; Goldstein, B.S.; Martin, K.; Makino, K.M.; Ismail, M.S.; Brand, C.; Mulnard, R.A.; Thai, G.; Mc Adams Ortiz, C.; Womack, K.; Mathews, D.; Quiceno, M.; Arrastia, R.D.; King, R.; Weiner, M.; Cook, K.M.; DeVous, M.; Levey, A.I.; Lah, J.J.; Cellar, J.S.; Burns, J.M.; Anderson, H.S.; Swerdlow, R.H.; Apostolova, L.; Tingus, K.; Woo, E.; Silverman, D.H.S.; Lu, P.H.; Bartzokis, G.; Radford, N.R.G.; Parfitt, F.; Kendall, T.; Johnson, H.; Farlow, M.R.; Hake, A.M.; Matthews, B.R.; Herring, S.; Hunt, C.; van Dyck, C.H.; Carson, R.E.; MacAvoy, M.G.; Chertkow, H.; Bergman, H.; Hosein, C.; Black, S.; Stefanovic, B.; Caldwell, C.; Hsiung, G.Y.R.; Feldman, H.; Mudge, B.; Past, M.A.; Kertesz, A.; Rogers, J.; Trost, D.; Bernick, C.; Munic, D.; Kerwin, D.; Mesulam, M.M.; Lipowski, K.; Wu, C.K.; Johnson, N.; Sadowsky, C.; Martinez, W.; Villena, T.; Turner, R.S.; Johnson, K.; Reynolds, B.; Sperling, R.A.; Johnson, K.A.; Marshall, G.; Frey, M.; Yesavage, J.; Taylor, J.L.; Lane, B.; Rosen, A.; Tinklenberg, J.; Sabbagh, M.N.; Belden, C.M.; Jacobson, S.A.; Sirrel, S.A.; Kowall, N.; Killiany, R.; Budson, A.E.; Norbash, A.; Johnson, P.L.; Obisesan, T.O.; Wolday, S.; Allard, J.; Lerner, A.; Ogrocki, P.; Hudson, L.; Fletcher, E.; Carmichael, O.; Olichney, J.; DeCarli, C.; Kittur, S.; Borrie, M.; Lee, T.Y.; Bartha, R.; Johnson, S.; Asthana, S.; Carlsson, C.M.; Potkin, S.G.; Preda, A.; Nguyen, D.; Tariot, P.; Fleisher, A.; Reeder, S.; Bates, V.; Capote, H.; Rainka, M.; Scharre, D.W.; Kataki, M.; Adeli, A.; Zimmerman, E.A.; Celmins, D.; Brown, A.D.; Pearlson, G.D.; Blank, K.; Anderson, K.; Santulli, R.B.; Kitzmiller, T.J.; Schwartz, E.S.; SinkS, K.M.; Williamson, J.D.; Garg, P.; Watkins, F.; Ott, B.R.; Querfurth, H.; Tremont, G.; Salloway, S.; Malloy, P.; Correia, S.; Rosen, H.J.; Miller, B.L.; Mintzer, J.; Spicer, K.; Bachman, D.; Finger, E.; Pasternak, S.; Rachinsky, I.; Rogers, J.; Kertesz, A.; Drost, D.; Pomara, N.; Hernando, R.; Sarrael, A.; Schultz, S.K.; Boles Ponto, L.L.; Shim, H.; Smith, K.E.; Relkin, N.; Chaing, G.; Raudin, L.; Smith, A.; Fargher, K.; Raj, B.A.; Andersson, E.; Berron, D.; Byman, E.; Sundberg-Brorsson, T.; Administrator; Borland, E.; Callmer, A.; Dahl, C.; Gertje, E.; Gustavsson, A-M.; Grzegorska, J.; Hall, S.; Hansson, O.; Insel, P.; Janelidze, S.; Johansson, M.; Sletten, H.; Jester-Broms, J.; Londos, E.; Mattson, N.; Minthon, L.; Nilsson, M.; Nordkvist, R.; Nägga, K.; Orbjörn, C.; Ossenkoppele, R.; Palmqvist, S.; Persson, M.; Santillo, A.; Spotorno, N.; Stomrud, E.; Toresson, H.; Strandberg, O.; Schöll, M.; Friberg, I.; Johansson, P.; Wibom, M.; Johansson, K.; Pettersson, E.; Karremo, C.; Smith, R.; Surova, Y.; Jalakas, M.; Lätt, J.; Mannfolk, P.; Nilsson, M.; Ståhlberg, F.; Sundgren, P.; van Westen, D.; Andreasson, U.; Blennow, K.; Zetterberg, H.; Wahlund, L-O.; Westman, E.; Pereira, J.; Jögi, J.; Hägerström, D.; Olsson, T.; Wollmer, P. Spread of pathological tau proteins through communicating neurons in human Alzheimer’s disease. Nat. Commun., 2020, 11(1), 2612.
[http://dx.doi.org/10.1038/s41467-020-15701-2] [PMID: 32457389]
[11]
Kayed, R.; Lasagna-Reeves, C.A. Molecular mechanisms of amyloid oligomers toxicity. J. Alzheimers Dis., 2012, 33(S1), S67-S78.
[http://dx.doi.org/10.3233/JAD-2012-129001] [PMID: 22531422]
[12]
Hassan, M.; Shahzadi, S.; Seo, S.Y.; Alashwal, H.; Zaki, N.; Moustafa, A.A. Molecular docking and dynamic simulation of azd3293 and solanezumab effects against bace1 to treat Alzheimer’s disease. Front. Comput. Neurosci., 2018, 12(6), 34.
[http://dx.doi.org/10.3389/fncom.2018.00034] [PMID: 29910719]
[13]
Lee, J.H.; Agacinski, G.; Williams, J.H.; Wilcock, G.K.; Esiri, M.M.; Francis, P.T.; Wong, P.T.H.; Chen, C.P.; Lai, M.K.P. Intact cannabinoid CB1 receptors in the Alzheimer’s disease cortex. Neurochem. Int., 2010, 57(8), 985-989.
[http://dx.doi.org/10.1016/j.neuint.2010.10.010] [PMID: 21034788]
[14]
Zhao, Y.; Zhao, B. Review article oxidative stress and the pathogenesis of Alzheimer’s Disease. Oxid. Med. Cell. Longev., 2013, 2013, 316523.
[http://dx.doi.org/10.1155/2013/316523] [PMID: 23983897]
[15]
Skaper, S.D. Alzheimer’s Disease and amyloid: Culprit or coincidence? Int. Rev. Neurobiol., 2012, 102, 277-316.
[http://dx.doi.org/10.1016/B978-0-12-386986-9.00011-9]
[16]
Tarkowski, E.; Andreasen, N.; Tarkowski, A.; Blennow, K. Intrathecal inflammation precedes development of Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry, 2003, 74(9), 1200-1205.
[http://dx.doi.org/10.1136/jnnp.74.9.1200] [PMID: 12933918]
[17]
DaRocha-Souto, B.; Scotton, T.C.; Coma, M.; Serrano-Pozo, A.; Hashimoto, T.; Serenó, L.; Rodríguez, M.; Sánchez, B.; Hyman, B.T.; Gómez-Isla, T. Brain oligomeric β-amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein/tau transgenic mice. J. Neuropathol. Exp. Neurol., 2011, 70(5), 360-376.
[http://dx.doi.org/10.1097/NEN.0b013e318217a118] [PMID: 21487307]
[18]
Pereira, C.F.; Santos, A.E.; Moreira, P.I.; Pereira, A.C.; Sousa, F.J.; Cardoso, S.M.; Cruz, M.T. Is Alzheimer’s disease an inflammasomopathy? Ageing Res. Rev., 2019, 56(8), 100966.
[http://dx.doi.org/10.1016/j.arr.2019.100966] [PMID: 31577960]
[19]
Kothari, V.; Luo, Y.; Tornabene, T.; O’Neill, A.M.; Greene, M.W.; Geetha, T.; Babu, J.R. High fat diet induces brain insulin resistance and cognitive impairment in mice. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(2), 499-508.
[http://dx.doi.org/10.1016/j.bbadis.2016.10.006] [PMID: 27771511]
[20]
Wei, L.; Yao, M.; Zhao, Z.; Jiang, H.; Ge, S. High-fat diet aggravates postoperative cognitive dysfunction in aged mice. BMC Anesthesiol., 2018, 18(1), 20.
[http://dx.doi.org/10.1186/s12871-018-0482-z] [PMID: 29439655]
[21]
Hermes, D.J.; Yadav-Samudrala, B.J.; Xu, C.; Paniccia, J.E.; Meeker, R.B.; Armstrong, M.L.; Reisdorph, N.; Cravatt, B.F.; Mackie, K.; Lichtman, A.H.; Ignatowska-Jankowska, B.M.; Lysle, D.T.; Fitting, S. GPR18 drives FAAH inhibition-induced neuroprotection against HIV-1 Tat-induced neurodegeneration. Exp. Neurol., 2021, 341(3), 113699.
[http://dx.doi.org/10.1016/j.expneurol.2021.113699] [PMID: 33736974]
[22]
Prillaman, M. Alzheimer’s drug slows mental decline in trial — but is it a breakthrough? Nature, 2022, 610(7930), 15-16.
[http://dx.doi.org/10.1038/d41586-022-03081-0] [PMID: 36175566]
[23]
Klyucherev, T.O.; Olszewski, P.; Shalimova, A.A.; Chubarev, V.N.; Tarasov, V.V.; Attwood, M.M.; Syvänen, S.; Schiöth, H.B. Advances in the development of new biomarkers for Alzheimer’s disease. Transl. Neurodegener., 2022, 11(1), 25.
[http://dx.doi.org/10.1186/s40035-022-00296-z] [PMID: 35449079]
[24]
Wang, Y.Y.; Sun, Y.P.; Luo, Y.M.; Peng, D.H.; Li, X.; Yang, B.Y.; Wang, Q.H.; Kuang, H.X. Biomarkers for the clinical diagnosis of Alzheimer’s Disease: Metabolomics analysis of brain tissue and blood. Front. Pharmacol., 2021, 12, 700587.
[http://dx.doi.org/10.3389/fphar.2021.700587] [PMID: 34366852]
[25]
Jack, C.R., Jr; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B.; Holtzman, D.M.; Jagust, W.; Jessen, F.; Karlawish, J.; Liu, E.; Molinuevo, J.L.; Montine, T.; Phelps, C.; Rankin, K.P.; Rowe, C.C.; Scheltens, P.; Siemers, E.; Snyder, H.M.; Sperling, R.; Elliott, C.; Masliah, E.; Ryan, L.; Silverberg, N. NIA‐AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement., 2018, 14(4), 535-562.
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[26]
Hampel, H.; Cummings, J.; Blennow, K.; Gao, P.; Jack, C.R., Jr; Vergallo, A. Developing the ATX(N) classification for use across the Alzheime’r disease continuum. Nat. Rev. Neurol., 2021, 17(9), 580-589.
[http://dx.doi.org/10.1038/s41582-021-00520-w] [PMID: 34239130]
[27]
Cummings, J.; Lee, G.; Nahed, P.; Kambar, M.E.Z.N.; Zhong, K.; Fonseca, J.; Taghva, K.; Taghva, K. Alzheimer’s disease drug development pipeline: 2022. Alzheimers Dement., 2022, 8(1), e12295.
[http://dx.doi.org/10.1002/trc2.12295] [PMID: 35516416]
[28]
Heneka, M.T.; Carson, M.J.; Khoury, J.E.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; Herrup, K.; Frautschy, S.A.; Finsen, B.; Brown, G.C.; Verkhratsky, A.; Yamanaka, K.; Koistinaho, J.; Latz, E.; Halle, A.; Petzold, G.C.; Town, T.; Morgan, D.; Shinohara, M.L.; Perry, V.H.; Holmes, C.; Bazan, N.G.; Brooks, D.J.; Hunot, S.; Joseph, B.; Deigendesch, N.; Garaschuk, O.; Boddeke, E.; Dinarello, C.A.; Breitner, J.C.; Cole, G.M.; Golenbock, D.T.; Kummer, M.P. Neuroinflammation in Alzheimer’s disease. Lancet Neurol., 2015, 14(4), 388-405.
[http://dx.doi.org/10.1016/S1474-4422(15)70016-5] [PMID: 25792098]
[29]
Minter, M.R.; Taylor, J.M.; Crack, P.J. The contribution of neuroinflammation to amyloid toxicity in Alzheimer’s disease. J. Neurochem., 2016, 136(3), 457-474.
[http://dx.doi.org/10.1111/jnc.13411] [PMID: 26509334]
[30]
Nimmerjahn, A.; Kirchhoff, F.; Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science, 2005, 308(5726), 1314-1318.
[http://dx.doi.org/10.1126/science.1110647] [PMID: 15831717]
[31]
Anwer, Z.; Gupta, S.P. A QSAR study on a series of pyrrole derivatives acting as lymphocyte-specific kinase (Lck) inhibitors. Med. Chem., 2012, 8(4), 649-655.
[http://dx.doi.org/10.2174/157340612801216319] [PMID: 22548340]
[32]
Jha, M.K.; Jo, M.; Kim, J.H.; Suk, K. Microglia-astrocyte crosstalk: An intimate molecular conversation. Neuroscientist, 2019, 25(3), 227-240.
[http://dx.doi.org/10.1177/1073858418783959] [PMID: 29931997]
[33]
Karch, C.M.; Goate, A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry, 2015, 77(1), 43-51.
[http://dx.doi.org/10.1016/j.biopsych.2014.05.006] [PMID: 24951455]
[34]
Galatro, T.F.; Holtman, I.R.; Lerario, A.M.; Vainchtein, I.D.; Brouwer, N.; Sola, P.R.; Veras, M.M.; Pereira, T.F.; Leite, R.E.P.; Möller, T.; Wes, P.D.; Sogayar, M.C.; Laman, J.D.; den Dunnen, W.; Pasqualucci, C.A.; Oba-Shinjo, S.M.; Boddeke, E.W.G.M.; Marie, S.K.N.; Eggen, B.J.L. Transcriptomic analysis of purified human cortical microglia reveals age-associated changes. Nat. Neurosci., 2017, 20(8), 1162-1171.
[http://dx.doi.org/10.1038/nn.4597] [PMID: 28671693]
[35]
Jay, T.R.; Von Saucken, V.E.; Landreth, G.E. TREM2 in neurodegenerative diseases. Mol. Neurodegener., 2017, 12(1), 1-33.
[http://dx.doi.org/10.1186/s13024-017-0197-5]
[36]
Lian, H.; Litvinchuk, A.; Chiang, A.C.A.; Aithmitti, N.; Jankowsky, J.L.; Zheng, H. Astrocyte-microglia cross talk through complement activation modulates amyloid pathology in mouse models of Alzheimer’s disease. J. Neurosci., 2016, 36(2), 577-589.
[http://dx.doi.org/10.1523/JNEUROSCI.2117-15.2016] [PMID: 26758846]
[37]
Arranz, A.M.; De Strooper, B. The role of astroglia in Alzheimer’s disease: Pathophysiology and clinical implications. Lancet Neurol., 2019, 18(4), 406-414.
[http://dx.doi.org/10.1016/S1474-4422(18)30490-3] [PMID: 30795987]
[38]
Spittau, B. Aging microglia—phenotypes, functions and implications for age-related neurodegenerative diseases. Front. Aging Neurosci., 2017, 9(6), 194.
[http://dx.doi.org/10.3389/fnagi.2017.00194] [PMID: 28659790]
[39]
Hanslik, K.L.; Ulland, T.K. The role of microglia and the Nlrp3 inflammasome in Alzheimer’s Disease. Front. Neurol., 2020, 11, 570711.
[http://dx.doi.org/10.3389/fneur.2020.570711] [PMID: 33071950]
[40]
Feng, Y.S.; Tan, Z.X.; Wu, L.Y.; Dong, F.; Zhang, F. The involvement of NLRP3 inflammasome in the treatment of Alzheimer’s disease. Ageing Res. Rev., 2020, 64, 101192.
[http://dx.doi.org/10.1016/j.arr.2020.101192] [PMID: 33059089]
[41]
Yu, Y.; Ye, R.D. Microglial Aβ receptors in Alzheimer’s disease. Cell. Mol. Neurobiol., 2015, 35(1), 71-83.
[http://dx.doi.org/10.1007/s10571-014-0101-6] [PMID: 25149075]
[42]
Li, Y.; Liu, L.; Barger, S.W.; Griffin, W.S.T. Interleukin-1 mediates pathological effects of microglia on tau phosphorylation and on synaptophysin synthesis in cortical neurons through a p38-MAPK pathway. J. Neurosci., 2003, 23(5), 1605-1611.
[http://dx.doi.org/10.1523/JNEUROSCI.23-05-01605.2003] [PMID: 12629164]
[43]
Angiulli, F.; Conti, E.; Zoia, C.P.; Da Re, F.; Appollonio, I.; Ferrarese, C.; Tremolizzo, L. Blood-based biomarkers of neuroinflammation in Alzheimer’s disease: A central role for periphery? Diagnostics, 2021, 11(9), 1525.
[http://dx.doi.org/10.3390/diagnostics11091525] [PMID: 34573867]
[44]
Hampel, H.; O’Bryant, S.E.; Molinuevo, J.L.; Zetterberg, H.; Masters, C.L.; Lista, S.; Kiddle, S.J.; Batrla, R.; Blennow, K. Blood-based biomarkers for Alzheimer disease: Mapping the road to the clinic. Nat. Rev. Neurol., 2018, 14(11), 639-652.
[http://dx.doi.org/10.1038/s41582-018-0079-7] [PMID: 30297701]
[45]
Shen, X.N.; Niu, L.D.; Wang, Y.J.; Cao, X.P.; Liu, Q.; Tan, L.; Zhang, C.; Yu, J.T. Inflammatory markers in Alzheimer’s disease and mild cognitive impairment: A meta-analysis and systematic review of 170 studies. J. Neurol. Neurosurg. Psychiatry, 2019, 90(5), 590-598.
[http://dx.doi.org/10.1136/jnnp-2018-319148] [PMID: 30630955]
[46]
Janelidze, S.; Hertze, J.; Zetterberg, H.; Landqvist Waldö, M.; Santillo, A.; Blennow, K.; Hansson, O. Cerebrospinal fluid neurogranin and YKL ‐40 as biomarkers of Alzheimer’s disease. Ann. Clin. Transl. Neurol., 2016, 3(1), 12-20.
[http://dx.doi.org/10.1002/acn3.266] [PMID: 26783546]
[47]
Janelidze, S.; Mattsson, N.; Stomrud, E.; Lindberg, O.; Palmqvist, S.; Zetterberg, H.; Blennow, K.; Hansson, O. CSF biomarkers of neuroinflammation and cerebrovascular dysfunction in early Alzheimer disease. Neurology, 2018, 91(9), e867-e877.
[http://dx.doi.org/10.1212/WNL.0000000000006082] [PMID: 30054439]
[48]
Jay, T.R.; Miller, C.M.; Cheng, P.J.; Graham, L.C.; Bemiller, S.; Broihier, M.L.; Xu, G.; Margevicius, D.; Karlo, J.C.; Sousa, G.L.; Cotleur, A.C.; Butovsky, O.; Bekris, L.; Staugaitis, S.M.; Leverenz, J.B.; Pimplikar, S.W.; Landreth, G.E.; Howell, G.R.; Ransohoff, R.M.; Lamb, B.T. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med., 2015, 212(3), 287-295.
[http://dx.doi.org/10.1084/jem.20142322] [PMID: 25732305]
[49]
Bemiller, S.M.; McCray, T.J.; Allan, K.; Formica, S.V.; Xu, G.; Wilson, G.; Kokiko-Cochran, O.N.; Crish, S.D.; Lasagna-Reeves, C.A.; Ransohoff, R.M.; Landreth, G.E.; Lamb, B.T. TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy. Mol. Neurodegener., 2017, 12(1), 74.
[http://dx.doi.org/10.1186/s13024-017-0216-6] [PMID: 29037207]
[50]
Bao, W.; Xie, F.; Zuo, C.; Guan, Y.; Huang, Y.H. PET neuroimaging of Alzheimer’s Disease: Radiotracers and their utility in clinical research. Front. Aging Neurosci., 2021, 13, 624330.
[http://dx.doi.org/10.3389/fnagi.2021.624330] [PMID: 34025386]
[51]
Gaetani, L.; Bellomo, G.; Parnetti, L.; Blennow, K.; Zetterberg, H.; Di Filippo, M. Neuroinflammation and Alzheimer’s Disease: A machine learning approach to CSF proteomics. Cells, 2021, 10(8), 1930.
[http://dx.doi.org/10.3390/cells10081930] [PMID: 34440700]
[52]
Bradburn, S.; Murgatroyd, C.; Ray, N. Neuroinflammation in mild cognitive impairment and Alzheimer’s disease: A meta-analysis. Ageing Res. Rev., 2019, 50, 1-8.
[http://dx.doi.org/10.1016/j.arr.2019.01.002] [PMID: 30610927]
[53]
Malpetti, M.; Kievit, R.A.; Passamonti, L.; Jones, P.S.; Tsvetanov, K.A.; Rittman, T.; Mak, E.; Nicastro, N.; Bevan-Jones, W.R.; Su, L.; Hong, Y.T.; Fryer, T.D.; Aigbirhio, F.I.; O’Brien, J.T.; Rowe, J.B. Microglial activation and tau burden predict cognitive decline in Alzheimer’s disease. Brain, 2020, 143(5), 1588-1602.
[http://dx.doi.org/10.1093/brain/awaa088] [PMID: 32380523]
[54]
Márquez, F.; Yassa, M.A. Neuroimaging biomarkers for Alzheimer’s Disease. Mol. Neurodegener., 2019, 14(1), 1-14.
[http://dx.doi.org/10.1186/s13024-019-0325-5]
[55]
Fu, W.Y.; Wang, X.; Ip, N.Y. Targeting neuroinflammation as a therapeutic strategy for Alzheimer’s Disease: Mechanisms, drug candidates, and new opportunities. ACS Chem. Neurosci., 2019, 10(2), 872-879.
[http://dx.doi.org/10.1021/acschemneuro.8b00402] [PMID: 30221933]
[56]
Althafar, Z.M. Targeting microglia in Alzheimer’s Disease: From molecular mechanisms to potential therapeutic targets for small molecules. Mol., 2022, 27(13), 4124.
[http://dx.doi.org/10.3390/molecules27134124]
[57]
Spangenberg, E.; Severson, P.L.; Hohsfield, L.A.; Crapser, J.; Zhang, J.; Burton, E.A.; Zhang, Y.; Spevak, W.; Lin, J.; Phan, N.Y.; Habets, G.; Rymar, A.; Tsang, G.; Walters, J.; Nespi, M.; Singh, P.; Broome, S.; Ibrahim, P.; Zhang, C.; Bollag, G.; West, B.L.; Green, K.N. Sustained microglial depletion with csf1r inhibitor impairs parenchymal plaque development in an Alzheimer’s Disease model. Nat. Commun., 2019, 10(1), 1-21.
[http://dx.doi.org/10.1038/s41467-019-11674-z]
[58]
Sosna, J.; Philipp, S.; Albay, R., III; Reyes-Ruiz, J.M.; Baglietto-Vargas, D.; LaFerla, F.M.; Glabe, C.G. Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease. Mol. Neurodegener., 2018, 13(1), 11.
[http://dx.doi.org/10.1186/s13024-018-0244-x]
[59]
Mancuso, R.; Van Den Daele, J.; Fattorelli, N.; Wolfs, L.; Balusu, S.; Burton, O.; Liston, A.; Sierksma, A.; Fourne, Y.; Poovathingal, S.; Arranz-Mendiguren, A.; Sala Frigerio, C.; Claes, C.; Serneels, L.; Theys, T.; Perry, V.H.; Verfaillie, C.; Fiers, M.; De Strooper, B. Stem-cell-derived human microglia transplanted in mouse brain to study human disease. Nat. Neurosci., 2019, 22(12), 2111-2116.
[http://dx.doi.org/10.1038/s41593-019-0525-x]
[60]
Muffat, J.; Li, Y.; Yuan, B.; Mitalipova, M.; Omer, A.; Corcoran, S.; Bakiasi, G.; Tsai, L.H.; Aubourg, P.; Ransohoff, R.M.; Jaenisch, R. Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat. Med., 2016, 22(11), 1358-1367.
[http://dx.doi.org/10.1038/nm.4189]
[61]
Douvaras, P.; Sun, B.; Wang, M.; Kruglikov, I.; Lallos, G.; Zimmer, M.; Terrenoire, C.; Zhang, B.; Gandy, S.; Schadt, E.; Freytes, D.O.; Noggle, S.; Fossati, V. Directed differentiation of human pluripotent stem cells to microglia. Stem Cell Reports, 2017, 8(6), 1516-1524.
[http://dx.doi.org/10.1016/j.stemcr.2017.04.023] [PMID: 28528700]
[62]
Price, B.R.; Sudduth, T.L.; Weekman, E.M.; Johnson, S.; Hawthorne, D.; Woolums, A.; Wilcock, D.M. Therapeutic Trem2 activation ameliorates amyloid-beta deposition and improves cognition in the 5XFAD model of amyloid deposition. J. Neuroinflammation, 2020, 17(1), 238.
[http://dx.doi.org/10.1186/s12974-020-01915-0] [PMID: 32795308]
[63]
Cheng, Q.; Danao, J.; Talreja, S.; Wen, P.; Yin, J.; Sun, N.; Li, C.M.; Chui, D.; Tran, D.; Koirala, S.; Chen, H.; Foltz, I.N.; Wang, S.; Sambashivan, S. TREM2-activating antibodies abrogate the negative pleiotropic effects of the Alzheimer’s disease variant Trem2R47H on murine myeloid cell function. J. Biol. Chem., 2018, 293(32), 12620-12633.
[http://dx.doi.org/10.1074/jbc.RA118.001848] [PMID: 29599291]
[64]
Miles, L.A.; Hermans, S.J.; Crespi, G.A.N.; Gooi, J.H.; Doughty, L.; Nero, T.L. Markulić J.; Ebneth, A.; Wroblowski, B.; Oehlrich, D.; Trabanco, A.A.; Rives, M.L.; Royaux, I.; Hancock, N.C.; Parker, M.W. small molecule binding to alzheimer risk factor CD33 promotes Aβ phagocytosis. iScience, 2019, 19, 110-118.
[http://dx.doi.org/10.1016/j.isci.2019.07.023] [PMID: 31369984]
[65]
Zhao, L. CD33 in Alzheimer’s Disease – biology, pathogenesis, and therapeutics: A Mini-Review. Gerontology, 2019, 65(4), 323-331.
[http://dx.doi.org/10.1159/000492596] [PMID: 30541012]
[66]
Heneka, M.T.; Sastre, M.; Dumitrescu-Ozimek, L.; Hanke, A.; Dewachter, I.; Kuiperi, C.; O’Banion, K.; Klockgether, T.; Van Leuven, F.; Landreth, G.E. Acute treatment with the PPARγ agonist pioglitazone and ibuprofen reduces glial inflammation and Aβ1–42 levels in APPV717I transgenic mice. Brain, 2005, 128(6), 1442-1453.
[http://dx.doi.org/10.1093/brain/awh452] [PMID: 15817521]
[67]
Wilkinson, B.L.; Cramer, P.E.; Varvel, N.H.; Reed-Geaghan, E.; Jiang, Q.; Szabo, A.; Herrup, K.; Lamb, B.T.; Landreth, G.E. Ibuprofen attenuates oxidative damage through NOX2 inhibition in Alzheimer’s disease. Neurobiol. Aging, 2012, 33(1), 197.e21-197.e32.
[http://dx.doi.org/10.1016/j.neurobiolaging.2010.06.014] [PMID: 20696495]
[68]
Geldmacher, D.S.; Fritsch, T.; McClendon, M.J.; Landreth, G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch. Neurol., 2011, 68(1), 45-50.
[http://dx.doi.org/10.1001/archneurol.2010.229] [PMID: 20837824]
[69]
Jiao, S.S.; Yao, X.Q.; Liu, Y.H.; Wang, Q.H.; Zeng, F.; Lu, J.J.; Liu, J.; Zhu, C.; Shen, L.L.; Liu, C.H.; Wang, Y.R.; Zeng, G.H.; Parikh, A.; Chen, J.; Liang, C.R.; Xiang, Y.; Bu, X.L.; Deng, J.; Li, J.; Xu, J.; Zeng, Y.Q.; Xu, X.; Xu, H.W.; Zhong, J.H.; Zhou, H.D.; Zhou, X.F.; Wang, Y.J. Edaravone alleviates Alzheimer’s Disease-type pathologies and cognitive deficits. Proc. Natl. Acad. Sci. USA, 2015, 112(16), 5225-5230.
[http://dx.doi.org/10.1073/pnas.1422998112] [PMID: 25847999]
[70]
Parikh, A.; Kathawala, K.; Li, J.; Chen, C.; Shan, Z.; Cao, X.; Wang, Y.J.; Garg, S.; Zhou, X.F. Self-nanomicellizing solid dispersion of edaravone: part II: In vivo assessment of efficacy against behavior deficits and safety in Alzheimer’s Disease model. Drug Des. Devel. Ther., 2018, 12, 2111-2128.
[http://dx.doi.org/10.2147/DDDT.S161944] [PMID: 30022810]
[71]
Howard, R.; Zubko, O.; Bradley, R.; Harper, E.; Pank, L.; O’Brien, J.; Fox, C.; Tabet, N.; Livingston, G.; Bentham, P.; McShane, R.; Burns, A.; Ritchie, C.; Reeves, S.; Lovestone, S.; Ballard, C.; Noble, W.; Nilforooshan, R.; Wilcock, G.; Gray, R. Minocycline at 2 different dosages vs. placebo for patients with mild alzheimer disease. JAMA Neurol., 2020, 77(2), 164-174.
[http://dx.doi.org/10.1001/jamaneurol.2019.3762] [PMID: 31738372]
[72]
Sharif, N.A. Degeneration of retina-brain components and connections in glaucoma: Disease causation and treatment options for eyesight preservation. Curr. Res. Neurobiol., 2022, 3, 100037.
[http://dx.doi.org/10.1016/j.crneur.2022.100037]
[73]
Thawkar, B.S.; Kaur, G. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: Novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. J. Neuroimmunol., 2019, 326, 62-74.
[http://dx.doi.org/10.1016/j.jneuroim.2018.11.010] [PMID: 30502599]
[74]
Illes, P. P2X7 Receptors amplify CNS damage in neurodegenerative diseases. Int. J. Mol. Sci., 2020, 21(17), 5996.
[http://dx.doi.org/10.3390/ijms21175996] [PMID: 32825423]
[75]
Stewart, W.F.; Kawas, C.; Corrada, M.; Metter, E.J. Risk of Alzheimer’s disease and duration of NSAID use. Neurology, 1997, 48(3), 626-632.
[http://dx.doi.org/10.1212/WNL.48.3.626] [PMID: 9065537]
[76]
Zandi, P.P.; Anthony, J.C.; Hayden, K.M.; Mehta, K.; Mayer, L.; Breitner, J.C.S. Reduced incidence of AD with NSAID but not H2 receptor antagonists: The Cache County Study. Neurology, 2002, 59(6), 880-886.
[http://dx.doi.org/10.1212/WNL.59.6.880] [PMID: 12297571]
[77]
Szekely, C.A.; Breitner, J.C.S.; Fitzpatrick, A.L.; Rea, T.D.; Psaty, B.M.; Kuller, L.H.; Zandi, P.P. NSAID use and dementia risk in the Cardiovascular Health Study: Role of APOE and NSAID type. Neurology, 2008, 70(1), 17-24.
[http://dx.doi.org/10.1212/01.wnl.0000284596.95156.48] [PMID: 18003940]
[78]
In ’T Veld, B. A.; Launer, L. J.; Hoes, A. W.; Ott, A.; Hofman, A.; Breteler, M. M. B.; Stricker, B. H. C. NSAIDs and Incident Alzheimer’s Disease. The Rotterdam Study. Neurobiol. Aging, 1998, 19(6), 607-611.
[http://dx.doi.org/10.1016/S0197-4580(98)00096-7] [PMID: 10192221]
[79]
Yip, A.G.; Green, R.C.; Huyck, M.; Cupples, L.A.; Farrer, L.A. Nonsteroidal anti-inflammatory drug use and Alzheimer’s Disease risk: the MIRAGE Study. BMC Geriatr., 2005, 5(1), 2.
[http://dx.doi.org/10.1186/1471-2318-5-2] [PMID: 15647106]
[80]
Mc Dowell, I.; Hill, G.; Lindsay, J.; Helliwell, B.; Costa, L.; Beattie, L.; Hertzman, C.; Tuokko, H.; Gutman, G.; Parhad, I.; Parboosingh, J.; Bland, R.; Newman, S.; Dobbs, A.; Hazlett, C.; Rule, B.; D’arcy, C.; Segall, A.; Chappell, N.; Manfreda, J.; Montgomery, P.; Østbye, T.; Robertson, J.; Hachinski, V.; Chambers, L.; Eastwood, R.; Rifat, S.; Verdon, J.; Nauarro, J.; Gauthier, S.; Wolfson, C.; Baumgarten, M.; Ska, B.; Joanette, Y.; Kergoat, M.J.; Nazerali, N.; Hébert, R.; Bravo, G.; Doyon, J.; Bouchard, R.; Morin, J.; Gauureau, D.; Balram, C.; Rockwood, K.; Gray, J.; Fisk, J.; Nilsson, T.; Donald, A.; Buehler, S.; Pryse-Phillips, W.; Kozma, A. The Canadian Study of Health and Aging: Risk factors for Alzheimer’s disease in Canada. Neurology, 1994, 44(11), 2073-2080.
[http://dx.doi.org/10.1212/WNL.44.11.2073] [PMID: 7969962]
[81]
Zhang, C.; Wang, Y.; Wang, D.; Zhang, J.; Zhang, F. NSAID exposure and risk of Alzheimer’s Disease: An updated meta-analysis from cohort studies. Front. Aging Neurosci., 2018, 10(3), 83.
[http://dx.doi.org/10.3389/fnagi.2018.00083] [PMID: 29643804]
[82]
Pasinetti, G.M. From epidemiology to therapeutic trials with anti-inflammatory drugs in Alzheimer’s disease: The role of NSAIDs and cyclooxygenase in β-amyloidosis and clinical dementia1. J. Alzheimers Dis., 2002, 4(5), 435-445.
[http://dx.doi.org/10.3233/JAD-2002-4510] [PMID: 12446975]
[83]
Liu, P.; Wang, Y.; Sun, Y.; Peng, G. Neuroinflammation as a Potential Therapeutic Target in Alzheimer’s Disease. Clin. Interv. Aging, 2022, 17, 665-674.
[http://dx.doi.org/10.2147/CIA.S357558] [PMID: 35520949]
[84]
Puhl, A.C.; Milton, F.A.; Cvoro, A.; Sieglaff, D.H.; Campos, J.C.L.; Bernardes, A.; Filgueira, C.S.; Lindemann, J.L.; Deng, T.; Neves, F.A.R.; Polikarpov, I.; Webb, P. Mechanisms of peroxisome proliferator activated receptor γ regulation by non-steroidal anti-inflammatory drugs. Nucl. Recept. Signal., 2015, 13(1), nrs.13004.
[http://dx.doi.org/10.1621/nrs.13004] [PMID: 26445566]
[85]
Athar, T.; Al Balushi, K.; Khan, S.A. Recent advances on drug development and emerging therapeutic agents for Alzheimer’s Disease. Mol. Biol. Rep., 2021, 48(7), 5629-5645.
[http://dx.doi.org/10.1007/s11033-021-06512-9] [PMID: 34181171]
[86]
Albertini, C.; Naldi, M.; Petralla, S.; Strocchi, S.; Grifoni, D.; Monti, B.; Bartolini, M.; Bolognesi, M.L. From combinations to single-molecule polypharmacology—cromolyn-ibuprofen conjugates for Alzheimer’s Disease. Mol., 2021, 26(4), 1112.
[http://dx.doi.org/10.3390/molecules26041112]
[87]
Sano, M.; Ernesto, C.; Thomas, R.G.; Klauber, M.R.; Schafer, K.; Grundman, M.; Woodbury, P.; Growdon, J.; Cotman, C.W.; Pfeiffer, E.; Schneider, L.S.; Thal, L.J. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s Disease. The Alzheimer’s Disease Cooperative Study. N. Engl. J. Med., 1997, 336(17), 1216-1222.
[http://dx.doi.org/10.1056/NEJM199704243361704] [PMID: 9110909]
[88]
Galluzzi, S.; Zanetti, O.; Binetti, G.; Trabucchi, M.; Frisoni, G.B. Coma in a patient with Alzheimer’s disease taking low dose trazodone and ginkgo biloba. J. Neurol. Neurosurg. Psychiatry, 2000, 68(5), 679a-680.
[http://dx.doi.org/10.1136/jnnp.68.5.679a] [PMID: 10836866]
[89]
SanMartín, C.D.; Henriquez, M.; Chacon, C.; Ponce, D.P.; Salech, F.; Rogers, N.K.; Behrens, M.I.; Vitamin, D. Vitamin D increases Aβ140 plasma levels and protects lymphocytes from oxidative death in mild cognitive impairment patients. Curr. Alzheimer Res., 2018, 15(6), 561-569.
[http://dx.doi.org/10.2174/1567205015666171227154636] [PMID: 29283046]
[90]
Annweiler, C.; Herrmann, F.R.; Fantino, B.; Brugg, B.; Beauchet, O. Effectiveness of the combination of memantine plus vitamin D on cognition in patients with Alzheimer disease: A pre-post pilot study. Cogn. Behav. Neurol., 2012, 25(3), 121-127.
[http://dx.doi.org/10.1097/WNN.0b013e31826df647] [PMID: 22960436]
[91]
Kontush, A.; Mann, U.; Arlt, S.; Ujeyl, A.; Lührs, C.; Müller-Thomsen, T.; Beisiegel, U. Influence of vitamin E and C supplementation on lipoprotein oxidation in patients with Alzheimer’s disease. Free Radic. Biol. Med., 2001, 31(3), 345-354.
[http://dx.doi.org/10.1016/S0891-5849(01)00595-0] [PMID: 11461772]
[92]
Dysken, M.W.; Sano, M.; Asthana, S.; Vertrees, J.E.; Pallaki, M.; Llorente, M.; Love, S.; Schellenberg, G.D.; McCarten, J.R.; Malphurs, J.; Prieto, S.; Chen, P.; Loreck, D.J.; Trapp, G.; Bakshi, R.S.; Mintzer, J.E.; Heidebrink, J.L.; Vidal-Cardona, A.; Arroyo, L.M.; Cruz, A.R.; Zachariah, S.; Kowall, N.W.; Chopra, M.P.; Craft, S.; Thielke, S.; Turvey, C.L.; Woodman, C.; Monnell, K.A.; Gordon, K.; Tomaska, J.; Segal, Y.; Peduzzi, P.N.; Guarino, P.D. Effect of vitamin E and memantine on functional decline in Alzheimer disease: The TEAM-AD VA cooperative randomized trial. JAMA, 2014, 311(1), 33-44.
[http://dx.doi.org/10.1001/jama.2013.282834] [PMID: 24381967]
[93]
Zhu, M.; Hao, S.; Liu, T.; Yang, L.; Zheng, P.; Zhang, L.; Ji, G. Lingguizhugan decoction improves non-alcoholic fatty liver disease by altering insulin resistance and lipid metabolism related genes: A whole trancriptome study by RNA-Seq. Oncotarget, 2017, 8(47), 82621-82631.
[http://dx.doi.org/10.18632/oncotarget.19734] [PMID: 29137289]
[94]
Breitner, J.; Baker, L.; Drye, L.; Evans, D.; Lyketsos, C.G.; Ryan, L.; Zandi, P.; Saucedo, H.H.; Anau, J.; Cholerton, B. Follow‐up evaluation of cognitive function in the randomized Alzheimer’s Disease Anti‐inflammatory Prevention Trial and its Follow‐up Study. Alzheimers Dement., 2015, 11(2), 216-25.e1.
[http://dx.doi.org/10.1016/j.jalz.2014.03.009] [PMID: 25022541]
[95]
Butchart, J.; Brook, L.; Hopkins, V.; Teeling, J.; Püntener, U.; Culliford, D.; Sharples, R.; Sharif, S.; McFarlane, B.; Raybould, R.; Thomas, R.; Passmore, P.; Perry, V.H.; Holmes, C. Etanercept in Alzheimer disease: A randomized, placebo-controlled, double-blind, phase 2 trial. Neurology, 2015, 84(21), 2161-2168.
[http://dx.doi.org/10.1212/WNL.0000000000001617] [PMID: 25934853]
[96]
Najem, D.; Bamji-Mirza, M.; Chang, N.; Liu, Q.Y.; Zhang, W. Insulin resistance, neuroinflammation, and Alzheimer’s disease. Rev. Neurosci., 2014, 25(4), 509-525.
[http://dx.doi.org/10.1515/revneuro-2013-0050] [PMID: 24622783]
[97]
El-Shiekh, R.A.; Ashour, R.M.; Abd El-Haleim, E.A.; Ahmed, K.A.; Abdel-Sattar, E. Hibiscus sabdariffa L.: A potent natural neuroprotective agent for the prevention of streptozotocin-induced Alzheimer’s disease in mice. Biomed. Pharmacother., 2020, 128(5), 110303.
[http://dx.doi.org/10.1016/j.biopha.2020.110303] [PMID: 32480228]
[98]
Combs, C.K.; Karlo, J.C.; Kao, S.C.; Landreth, G.E. beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J. Neurosci., 2001, 21(4), 1179-1188.
[http://dx.doi.org/10.1523/JNEUROSCI.21-04-01179.2001] [PMID: 11160388]
[99]
Liao, Y.F.; Wang, B.J.; Cheng, H.T.; Kuo, L.H.; Wolfe, M.S. Tumor necrosis factor-α interleukin-1β and interferon-γ stimulate γ-secretase-mediated cleavage of amyloid precursor protein through a JNK-dependent MAPK pathway. J. Biol. Chem., 2004, 279(47), 49523-49532.
[http://dx.doi.org/10.1074/jbc.M402034200] [PMID: 15347683]
[100]
Chen, G.; Goeddel, D.V. TNF-R1 signaling: A beautiful pathway. Science, 2002, 296(5573), 1634-1635.
[http://dx.doi.org/10.1126/science.1071924] [PMID: 12040173]
[101]
Torres-Acosta, N.; O’Keefe, J.H.; O’Keefe, E.L.; Isaacson, R.; Small, G. Therapeutic Potential of TNF-α Inhibition for Alzheimer’s Disease Prevention. J. Alzheimers Dis., 2020, 78(2), 619-626.
[http://dx.doi.org/10.3233/JAD-200711] [PMID: 33016914]
[102]
Shi, J.Q.; Shen, W.; Chen, J.; Wang, B.R.; Zhong, L.L.; Zhu, Y.W.; Zhu, H.Q.; Zhang, Q.Q.; Zhang, Y.D.; Xu, J. Anti-TNF-α reduces amyloid plaques and tau phosphorylation and induces CD11c-positive dendritic-like cell in the APP/PS1 transgenic mouse brains. Brain Res., 2011, 1368, 239-247.
[http://dx.doi.org/10.1016/j.brainres.2010.10.053] [PMID: 20971085]
[103]
Kim, D.H.; Choi, S.M.; Jho, J.; Park, M.S.; Kang, J.; Park, S.J.; Ryu, J.H.; Jo, J.; Kim, H.H.; Kim, B.C. Infliximab ameliorates AD-associated object recognition memory impairment. Behav. Brain Res., 2016, 311, 384-391.
[http://dx.doi.org/10.1016/j.bbr.2016.06.001] [PMID: 27265784]
[104]
Ou, W.; Yang, J.; Simanauskaite, J.; Choi, M.; Castellanos, D.M.; Chang, R.; Sun, J.; Jagadeesan, N.; Parfitt, K.D.; Cribbs, D.H.; Sumbria, R.K. Biologic TNF-α inhibitors reduce microgliosis, neuronal loss, and tau phosphorylation in a transgenic mouse model of tauopathy. J. Neuroinflam., 2021, 18(1), 312.
[http://dx.doi.org/10.1186/s12974-021-02332-7] [PMID: 34972522]
[105]
Boado, R.J.; Hui, E.K.W.; Lu, J.Z.; Zhou, Q.H.; Pardridge, W.M. Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein. J. Biotechnol., 2010, 146(1-2), 84-91.
[http://dx.doi.org/10.1016/j.jbiotec.2010.01.011] [PMID: 20100527]
[106]
Tobinick, E.; Gross, H.; Weinberger, A.; Cohen, H. TNF-alpha modulation for treatment of Alzheimer’s Disease: A 6-month pilot study. MedGenMed, 2006, 8(2), 25.
[PMID: 16926764]
[107]
Atigari, O.V.; Healy, D. Schizophrenia-like disorder associated with etanercept treatment. BMJ Case Rep., 2014, 2014(1), bcr2013200464.
[http://dx.doi.org/10.1136/bcr-2013-200464] [PMID: 24419811]
[108]
Roerink, M.E.; Groen, R.J.M.; Franssen, G.; Lemmers-van de Weem, B.; Boerman, O.C.; van der Meer, J.W.M. Central delivery of iodine-125–labeled cetuximab, etanercept and anakinra after perispinal injection in rats: Possible implications for treating Alzheimer’s disease. Alzheimers Res. Ther., 2015, 7(1), 70.
[http://dx.doi.org/10.1186/s13195-015-0149-7] [PMID: 26560086]
[109]
Zhou, M.; Xu, R.; Kaelber, D.C.; Gurney, M.E. Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis. PLoS One, 2020, 15(3), e0229819.
[http://dx.doi.org/10.1371/journal.pone.0229819] [PMID: 32203525]
[110]
Dong, Y.; Fischer, R.; Naudé, P.J.W.; Maier, O.; Nyakas, C.; Duffey, M.; Van der Zee, E.A.; Dekens, D.; Douwenga, W.; Herrmann, A.; Guenzi, E.; Kontermann, R.E.; Pfizenmaier, K.; Eisel, U.L.M. Essential protective role of tumor necrosis factor receptor 2 in neurodegeneration. Proc. Natl. Acad. Sci., 2016, 113(43), 12304-12309.
[http://dx.doi.org/10.1073/pnas.1605195113] [PMID: 27791020]
[111]
MacPherson, K.P.; Sompol, P.; Kannarkat, G.T.; Chang, J.; Sniffen, L.; Wildner, M.E.; Norris, C.M.; Tansey, M.G. Peripheral administration of the soluble TNF inhibitor XPro1595 modifies brain immune cell profiles, decreases beta-amyloid plaque load, and rescues impaired long-term potentiation in 5xFAD mice. Neurobiol. Dis., 2017, 102, 81-95.
[http://dx.doi.org/10.1016/j.nbd.2017.02.010] [PMID: 28237313]
[112]
Vieira, M. N. N.; Lima-Filho, R. A. S.; De Felice, F. G. Connecting Alzheimer’s Disease to diabetes: Underlying mechanisms and potential therapeutic targets. Neuropharmacology, 2018, 136(Pt B), 160-171.
[http://dx.doi.org/10.1016/j.neuropharm.2017.11.014]
[113]
Frisardi, V.; Solfrizzi, V.; Seripa, D.; Capurso, C.; Santamato, A.; Sancarlo, D.; Vendemiale, G.; Pilotto, A.; Panza, F. Metabolic-cognitive syndrome: A cross-talk between metabolic syndrome and Alzheimer’s disease. Ageing Res. Rev., 2010, 9(4), 399-417.
[http://dx.doi.org/10.1016/j.arr.2010.04.007] [PMID: 20444434]
[114]
Kullmann, S.; Heni, M.; Hallschmid, M.; Fritsche, A.; Preissl, H.; Häring, H.U. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol. Rev., 2016, 96(4), 1169-1209.
[http://dx.doi.org/10.1152/physrev.00032.2015] [PMID: 27489306]
[115]
Kianpour Rad, S.; Arya, A.; Karimian, H.; Madhavan, P.; Rizwan, F.; Koshy, S.; Prabhu, G. Mechanism involved in insulin resistance via accumulation of β-amyloid and neurofibrillary tangles: Link between type 2 diabetes and Alzheimer’s Disease. Drug Des. Devel. Ther., 2018, 12, 3999-4021.
[http://dx.doi.org/10.2147/DDDT.S173970] [PMID: 30538427]
[116]
Marciniak, E.; Leboucher, A.; Caron, E.; Ahmed, T.; Tailleux, A.; Dumont, J.; Issad, T.; Gerhardt, E.; Pagesy, P.; Vileno, M.; Bournonville, C.; Hamdane, M.; Bantubungi, K.; Lancel, S.; Demeyer, D.; Eddarkaoui, S.; Vallez, E.; Vieau, D.; Humez, S.; Faivre, E.; Grenier-Boley, B.; Outeiro, T.F.; Staels, B.; Amouyel, P.; Balschun, D.; Buee, L.; Blum, D. Tau deletion promotes brain insulin resistance. J. Exp. Med., 2017, 214(8), 2257-2269.
[http://dx.doi.org/10.1084/jem.20161731] [PMID: 28652303]
[117]
Rodriguez-Rodriguez, P.; Sandebring-Matton, A.; Merino-Serrais, P.; Parrado-Fernandez, C.; Rabano, A.; Winblad, B.; Ávila, J.; Ferrer, I.; Cedazo-Minguez, A. Tau hyperphosphorylation induces oligomeric insulin accumulation and insulin resistance in neurons. Brain, 2017, 140(12), 3269-3285.
[http://dx.doi.org/10.1093/brain/awx256] [PMID: 29053786]
[118]
Luque-Contreras, D.; Carvajal, K.; Toral-Rios, D.; Franco-Bocanegra, D.; Campos-Peña, V. Oxidative stress and metabolic syndrome: cause or consequence of Alzheimer’s Disease? Oxid. Med. Cell. Longev., 2014, 2014, 1-11.
[http://dx.doi.org/10.1155/2014/497802] [PMID: 24683436]
[119]
De Felice, F.G.; Lourenco, M.V.; Ferreira, S.T. How does brain insulin resistance develop in Alzheimer’s Disease? Alzheimers Dement., 2014, 10(1S)(Suppl.), S26-S32.
[http://dx.doi.org/10.1016/j.jalz.2013.12.004] [PMID: 24529521]
[120]
Zhou, Y.L.; Du, Y.F.; Du, H.; Shao, P. Insulin resistance in Alzheimer’s disease (AD) mouse intestinal macrophages is mediated by activation of JNK. Eur. Rev. Med. Pharmacol. Sci., 2017, 21(8), 1787-1794.
[PMID: 28485801]
[121]
Peng, Y.; Gao, P.; Shi, L.; Chen, L.; Liu, J.; Long, J. Central and peripheral metabolic defects contribute to the pathogenesis of alzheimer’s disease: Targeting mitochondria for diagnosis and prevention. Antioxid. Redox Signal., 2020, 32(16), 1188-1236.
[http://dx.doi.org/10.1089/ars.2019.7763] [PMID: 32050773]
[122]
Kinney, J.W.; Bemiller, S.M.; Murtishaw, A.S.; Leisgang, A.M.; Salazar, A.M.; Lamb, B.T. Inflammation as a central mechanism in Alzheimer’s Disease. Alzheimers Dement., 2018, 4(1), 575-590.
[http://dx.doi.org/10.1016/j.trci.2018.06.014] [PMID: 30406177]
[123]
Spinelli, M.; Fusco, S.; Grassi, C. Brain insulin resistance and hippocampal plasticity: Mechanisms and biomarkers of cognitive decline. Front. Neurosci., 2019, 13, 788.
[http://dx.doi.org/10.3389/fnins.2019.00788] [PMID: 31417349]
[124]
Kern, W.; Peters, A.; Fruehwald-Schultes, B.; Deininger, E.; Born, J.; Fehm, H.L. Improving influence of insulin on cognitive functions in humans. Neuroendocrinology, 2001, 74(4), 270-280.
[http://dx.doi.org/10.1159/000054694] [PMID: 11598383]
[125]
Kern, W.; Born, J.; Schreiber, H.; Fehm, H.L. Central nervous system effects of intranasally administered insulin during euglycemia in men. Diabetes, 1999, 48(3), 557-563.
[http://dx.doi.org/10.2337/diabetes.48.3.557] [PMID: 10078556]
[126]
Avgerinos, K.I.; Kalaitzidis, G.; Malli, A.; Kalaitzoglou, D.; Myserlis, P.G.; Lioutas, V.A. Intranasal insulin in Alzheimer’s Dementia or mild cognitive impairment: A systematic review. J. Neurol., 2018, 265(7), 1497-1510.
[http://dx.doi.org/10.1007/s00415-018-8768-0] [PMID: 29392460]
[127]
Kamal, R.M.; Razis, A.F.A.; Sukri, N.S.M.; Perimal, E.K.; Ahmad, H.; Patrick, R.; Djedaini-Pilard, F.; Mazzon, E.; Rigaud, S. Beneficial health effects of glucosinolates-derived isothiocyanates on cardiovascular and neurodegenerative diseases. Mol., 2022, 27(3), 624.
[http://dx.doi.org/10.3390/molecules27030624]
[128]
Candeias, E.M.; Sebastião, I.C.; Cardoso, S.M.; Correia, S.C.; Carvalho, C.I.; Plácido, A.I.; Santos, M.S.; Oliveira, C.R.; Moreira, P.I.; Duarte, A.I. Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide. World J. Diabetes, 2015, 6(6), 807-827.
[http://dx.doi.org/10.4239/wjd.v6.i6.807] [PMID: 26131323]
[129]
Makita, K.; Takahashi, K.; Karara, A.; Jacobson, H.R.; Falck, J.R.; Capdevila, J.H. Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. J. Clin. Invest., 1994, 94(6), 2414-2420.
[http://dx.doi.org/10.1172/JCI117608] [PMID: 7989598]
[130]
Gault, V.A.; Porter, W.D.; Flatt, P.R.; Hölscher, C. Actions of exendin-4 therapy on cognitive function and hippocampal synaptic plasticity in mice fed a high-fat diet. Int. J. Obes., 2010, 34(8), 1341-1344.
[http://dx.doi.org/10.1038/ijo.2010.59] [PMID: 20351729]
[131]
Hamilton, A.; Patterson, S.; Porter, D.; Gault, V.A.; Holscher, C. Novel GLP-1 mimetics developed to treat type 2 diabetes promote progenitor cell proliferation in the brain. J. Neurosci. Res., 2011, 89(4), 481-489.
[http://dx.doi.org/10.1002/jnr.22565] [PMID: 21312223]
[132]
Gold, M.; Alderton, C.; Zvartau-Hind, M.; Egginton, S.; Saunders, A.M.; Irizarry, M.; Craft, S.; Landreth, G.; Linnamägi, Ü.; Sawchak, S. Rosiglitazone monotherapy in mild-to-moderate Alzheimer’s disease: Results from a randomized, double-blind, placebo-controlled phase III study. Dement. Geriatr. Cogn. Disord., 2010, 30(2), 131-146.
[http://dx.doi.org/10.1159/000318845] [PMID: 20733306]
[133]
Harrington, C.; Sawchak, S.; Chiang, C.; Davies, J.; Donovan, C.; Saunders, A.M.; Irizarry, M.; Jeter, B.; Zvartau-Hind, M.; van Dyck, C.H.; Gold, M. Rosiglitazone does not improve cognition or global function when used as adjunctive therapy to AChE inhibitors in mild-to-moderate Alzheimer’s disease: Two phase 3 studies. Curr. Alzheimer Res., 2011, 8(5), 592-606.
[http://dx.doi.org/10.2174/156720511796391935] [PMID: 21592048]
[134]
Koenig, A.M.; Mechanic-Hamilton, D.; Xie, S.X.; Combs, M.F.; Cappola, A.R.; Xie, L.; Detre, J.A.; Wolk, D.A.; Arnold, S.E. Effects of the Insulin Sensitizer Metformin in Alzheimer Disease. Alzheimer Dis. Assoc. Disord., 2017, 31(2), 107-113.
[http://dx.doi.org/10.1097/WAD.0000000000000202] [PMID: 28538088]
[135]
Rivera, P.; Fernández-Arjona, M.M.; Silva-Peña, D.; Blanco, E.; Vargas, A.; López-Ávalos, M.D.; Grondona, J.M.; Serrano, A.; Pavón, F.J.; Rodríguez de Fonseca, F.; Suárez, J. Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves memory and changes the phenotype of hippocampal microglia despite ethanol exposure. Biochem. Pharmacol., 2018, 157, 244-257.
[http://dx.doi.org/10.1016/j.bcp.2018.08.005] [PMID: 30098312]
[136]
Mulder, J.; Zilberter, M.; Pasquaré, S.J.; Alpár, A.; Schulte, G.; Ferreira, S.G.; Köfalvi, A.; Martín-Moreno, A.M.; Keimpema, E.; Tanila, H.; Watanabe, M.; Mackie, K.; Hortobágyi, T.; de Ceballos, M.L.; Harkany, T. Molecular reorganization of endocannabinoid signalling in Alzheimer’s Disease. Brain, 2011, 134(4), 1041-1060.
[http://dx.doi.org/10.1093/brain/awr046] [PMID: 21459826]
[137]
Mohamed, W.A.; Salama, R.M.; Schaalan, M.F. A pilot study on the effect of lactoferrin on Alzheimer’s Disease pathological sequelae: Impact of the p-Akt/PTEN pathway. Biomed. Pharmacother., 2019, 111(111), 714-723.
[http://dx.doi.org/10.1016/j.biopha.2018.12.118] [PMID: 30611996]
[138]
Abdelhamid, M.; Jung, C.G.; Zhou, C.; Abdullah, M.; Nakano, M.; Wakabayashi, H.; Abe, F.; Michikawa, M. Dietary lactoferrin supplementation prevents memory impairment and reduces amyloid-β generation in J20 mice. J. Alzheimers Dis., 2020, 74(1), 245-259.
[http://dx.doi.org/10.3233/JAD-191181] [PMID: 31985470]
[139]
Wink, M.; Ashour, M.L.; Youssef, F.S.; Gad, H.A. Inhibition of cytochrome P450 (CYP3A4) activity by extracts from 57 plants used in traditional chinese medicine (TCM). Pharmacogn. Mag., 2017, 13(50), 300-308.
[http://dx.doi.org/10.4103/0973-1296.204561] [PMID: 28539725]
[140]
Staehelin, H.B. Micronutrients and Alzheimer’s Disease. Proc. Nutr. Soc., 2005, 64(4), 565-570.
[http://dx.doi.org/10.1079/PNS2005459] [PMID: 16313699]
[141]
Cichon, N.; Dziedzic, A.; Gorniak, L.; Miller, E.; Bijak, M.; Starosta, M.; Saluk-Bijak, J. Unusual bioactive compounds with antioxidant properties in adjuvant therapy supporting cognition impairment in age-related neurodegenerative disorders. Int. J. Mol. Sci., 2021, 22(19), 10707.
[http://dx.doi.org/10.3390/ijms221910707] [PMID: 34639048]
[142]
Liu, J.; Li, H.; Gong, T.; Chen, W.; Mao, S.; Kong, Y.; Yu, J.; Sun, J. Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer’s Disease via upregulating GPR41 and Inhibiting ERK/JNK/NF-κ. B. J. Agric. Food Chem., 2020, 68(27), 7152-7161.
[http://dx.doi.org/10.1021/acs.jafc.0c02807] [PMID: 32583667]
[143]
Vashistha, P.; Zahra, K.; Kumar, A.; Kumar, T.; Srivastava, M.; Mishra, S.P. Is there a correlation between micronutrients and cognitive status: an exploratory study of senile dementia of Alzheimer’s Type. J. Clin. Diagn. Res., 2018, 12(4), BC01-BC04.
[http://dx.doi.org/10.7860/JCDR/2018/32236.11376]
[144]
Park, S.; Kang, S.; Sol Kim, D. Folate and vitamin B-12 deficiencies additively impaire memory function and disturb the gut microbiota in amyloid-β infused rats. Int. J. Vitam. Nutr. Res., 2022, 92(3-4), 169-181.
[http://dx.doi.org/10.1024/0300-9831/a000624] [PMID: 31841076]
[145]
Ma, F.; Zhou, X.; Li, Q.; Zhao, J.; Song, A.; An, P.; Du, Y.; Xu, W.; Huang, G. Effects of folic acid and vitamin B12, alone and in combination on cognitive function and inflammatory factors in the elderly with mild cognitive impairment: A single-blind experimental design. Curr. Alzheimer Res., 2019, 16(7), 622-632.
[http://dx.doi.org/10.2174/1567205016666190725144629] [PMID: 31345146]
[146]
Vakilian, A.; Razavi-Nasab, S.M.; Ravari, A.; Mirzaei, T.; Moghadam-Ahmadi, A.; Jalali, N.; Bahramabadi, R.; Rezayati, M.; Yazdanpanah-Ravari, A.; Bahmaniar, F.; Bagheri, M.R.; Sheikh Fathollahi, M.; Asadikaram, G. Kazemi arababadi, m. vitamin B12 in association with antipsychotic drugs can modulate the expression of pro-/anti-inflammatory cytokines in Alzheimer Disease Patients. Neuroimmunomodulation, 2017, 24(6), 310-319.
[http://dx.doi.org/10.1159/000486597] [PMID: 29558759]
[147]
Bahramabadi, R.; Samadi, M.; Vakilian, A.; Jafari, E.; Fathollahi, M.S.; Arababadi, M.K. Evaluation of the effects of anti-psychotic drugs on the expression of CD68 on the peripheral blood monocytes of Alzheimer patients with psychotic symptoms. Life Sci., 2017, 179, 73-79.
[http://dx.doi.org/10.1016/j.lfs.2017.04.024] [PMID: 28465247]
[148]
Ramprasad, M.P.; Terpstra, V.; Kondratenko, N.; Quehenberger, O.; Steinberg, D. Cell surface expression of mouse macrosialin and human CD68 and their role as macrophage receptors for oxidized low density lipoprotein. Proc. Natl. Acad. Sci. USA, 1996, 93(25), 14833-14838.
[http://dx.doi.org/10.1073/pnas.93.25.14833] [PMID: 8962141]
[149]
Cabezas-Cerrato, J.; Garcia-Estevez, D.A.; Araújo, D.; Iglesias, M. Insulin sensitivity, glucose effectiveness, and β-cell function in obese males with essential hypertension: Investigation of the effects of treatment with a calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor (quinapril). Metabolism, 1997, 46(2), 173-178.
[http://dx.doi.org/10.1016/S0026-0495(97)90298-5] [PMID: 9030825]
[150]
Farah, R.; Khamisy-Farah, R.; Shurtz-Swirski, R. Calcium channel blocker effect on insulin resistance and inflammatory markers in essential hypertension patients. Int. Angiol., 2013, 32(1), 85-93.
[PMID: 23435396]
[151]
Li, X.; Wang, L.; Gao, X.; Li, G.; Cao, H.; Song, D.; Cai, S.; Liang, T.; Zhang, B.; Du, G. Mechanisms of protective effect of ramulus mori polysaccharides on renal injury in high-fat diet/streptozotocin-induced diabetic rats. Cell. Physiol. Biochem., 2015, 37(6), 2125-2134.
[http://dx.doi.org/10.1159/000438570] [PMID: 26599870]
[152]
Schmidt, M.E.; Liebowitz, M.R.; Stein, M.B.; Grunfeld, J.; Van Hove, I.; Simmons, W.K.; Van Der Ark, P.; Palmer, J.A.; Saad, Z.S.; Pemberton, D.J.; Van Nueten, L.; Drevets, W.C. The effects of inhibition of fatty acid amide hydrolase (FAAH) by JNJ-42165279 in social anxiety disorder: A double-blind, randomized, placebo-controlled proof-of-concept study. Neuropsychopharmacology, 2021, 46(5), 1004-1010.
[http://dx.doi.org/10.1038/s41386-020-00888-1] [PMID: 33070154]
[153]
Lawlor, B.; Segurado, R.; Kennelly, S.; Olde Rikkert, M.G.M.; Howard, R.; Pasquier, F.; Börjesson-Hanson, A.; Tsolaki, M.; Lucca, U.; Molloy, D.W.; Coen, R.; Riepe, M.W.; Kálmán, J.; Kenny, R.A.; Cregg, F.; O’Dwyer, S.; Walsh, C.; Adams, J.; Banzi, R.; Breuilh, L.; Daly, L.; Hendrix, S.; Aisen, P.; Gaynor, S.; Sheikhi, A.; Taekema, D.G.; Verhey, F.R.; Nemni, R.; Nobili, F.; Franceschi, M.; Frisoni, G.; Zanetti, O.; Konsta, A.; Anastasios, O.; Nenopoulou, S.; Tsolaki-Tagaraki, F.; Pakaski, M.; Dereeper, O.; de la Sayette, V.; Sénéchal, O.; Lavenu, I.; Devendeville, A.; Calais, G.; Crawford, F.; Mullan, M. Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial. PLoS Med., 2018, 15(9), e1002660.
[http://dx.doi.org/10.1371/journal.pmed.1002660] [PMID: 30248105]
[154]
Huang, W.; Li, Z.; Zhao, L.; Zhao, W. Simvastatin ameliorate memory deficits and inflammation in clinical and mouse model of Alzheimer’s disease via modulating the expression of miR-106b. Biomed. Pharmacother., 2017, 92, 46-57.
[http://dx.doi.org/10.1016/j.biopha.2017.05.060] [PMID: 28528185]
[155]
Zhao, L.; Zhao, Q.; Zhou, Y.; Zhao, Y.; Wan, Q. Atorvastatin may correct dyslipidemia in adult patients at risk for alzheimer’s disease through an anti-inflammatory pathway. CNS Neurol. Disord. Drug Targets, 2016, 15(1), 80-85.
[http://dx.doi.org/10.2174/1871527315999160111160143] [PMID: 26666876]
[156]
Ferrari, J. Randomized Controlled Trial of Atorvastatin in Mild to Moderate Alzheimer Disease: LEADe. J. Neurol. Neurochir. Psychiatr., 2010, 11(4), 85.
[157]
Poly, T.N.; Islam, M.M.; Walther, B.A.; Yang, H.C.; Wu, C.C.; Lin, M.C.; Li, Y.C. Association between use of statin and risk of dementia: A meta-analysis of observational studies. Neuroepidemiology, 2020, 54(3), 214-226.
[http://dx.doi.org/10.1159/000503105] [PMID: 31574510]
[158]
Sano, M.; Bell, K.L.; Galasko, D.; Galvin, J.E.; Thomas, R.G.; van Dyck, C.H.; Aisen, P.S. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology, 2011, 77(6), 556-563.
[http://dx.doi.org/10.1212/WNL.0b013e318228bf11] [PMID: 21795660]
[159]
Lin, Z.; Vicente Gonçalves, C.M.; Dai, L.; Lu, H.; Huang, J.; Ji, H.; Wang, D.; Yi, L.; Liang, Y. Exploring metabolic syndrome serum profiling based on gas chromatography mass spectrometry and random forest models. Anal. Chim. Acta, 2014, 827, 22-27.
[http://dx.doi.org/10.1016/j.aca.2014.04.008] [PMID: 24832990]
[160]
van den Elsen, G.A.H.; Ahmed, A.I.A.; Verkes, R.J.; Kramers, C.; Feuth, T.; Rosenberg, P.B.; van der Marck, M.A.; Olde Rikkert, M.G.M.; Aiaa, T. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia a randomized controlled trial. G. Am. Acad. Neurol., 2015, 84(23), 2338-2346.
[http://dx.doi.org/10.1212/WNL.0000000000001675] [PMID: 25972490]
[161]
Bilginer, S.; Anil, B.; Koca, M.; Demir, Y.; Gülçin, I. novel mannich bases with strong carbonic anhydrases and acetylcholinesterase inhibition effects: 3-(Aminomethyl)-6-{3-[4-(Trifluoromethyl)Phenyl]Acryloyl}-2(3H)-. Benzoxazolones. Turk. J. Chem., 2021, 45(3), 805-818.
[http://dx.doi.org/10.3906/kim-2101-25] [PMID: 34385868]
[162]
Oboh, G.; Adedayo, B.C.; Adetola, M.B.; Oyeleye, I.S.; Ogunsuyi, O.B. Characterization and neuroprotective properties of alkaloid extract of Vernonia amygdalina Delile in experimental models of Alzheimer’s disease. Drug Chem. Toxicol., 2022, 45(2), 731-740.
[http://dx.doi.org/10.1080/01480545.2020.1773845] [PMID: 32543989]
[163]
Himalian, R.; Singh, S.K.; Singh, M.P. Ameliorative Role of Nutraceuticals on Neurodegenerative Diseases Using the Drosophila Melanogaster as a Discovery Model to Define Bioefficacy. J. Am. Nutr. Assoc., 2022, 14(5), 511-539.
[http://dx.doi.org/10.1080/07315724.2021.1904305] [PMID: 34125661]
[164]
Sadhukhan, P.; Saha, S.; Dutta, S.; Mahalanobish, S.; Sil, P.C. Nutraceuticals: An emerging therapeutic approach against the pathogenesis of Alzheimer’s Disease; Elsevier Ltd., 2018, p. 129.
[http://dx.doi.org/10.1016/j.phrs.2017.11.028]
[165]
Mori, T.; Koyama, N.; Tan, J.; Segawa, T.; Maeda, M.; Town, T. Combined treatment with the phenolics (−)-epigallocatechin-3-gallate and ferulic acid improves cognition and reduces Alzheimer-like pathology in mice. J. Biol. Chem., 2019, 294(8), 2714-5444.
[http://dx.doi.org/10.1074/jbc.RA118.004280] [PMID: 30563837]
[166]
Pandareesh, M.D.; Chauhan, V.; Chauhan, A. Walnut Supplementation in the Diet Reduces Oxidative Damage and Improves Antioxidant Status in Transgenic Mouse Model of Alzheimer’s Disease. J. Alzheimers Dis., 2018, 64(4), 1295-1305.
[http://dx.doi.org/10.3233/JAD-180361] [PMID: 30040727]
[167]
Rainey-Smith, S.R.; Brown, B.M.; Sohrabi, H.R.; Shah, T.; Goozee, K.G.; Gupta, V.B.; Martins, R.N. Curcumin and cognition: A randomised, placebo-controlled, double-blind study of community-dwelling older adults. Br. J. Nutr., 2016, 115(12), 2106-2113.
[http://dx.doi.org/10.1017/S0007114516001203] [PMID: 27102361]
[168]
Malhotra, A.; Bath, S.; Elbarbry, F. An organ system approach to explore the antioxidative, anti-inflammatory and cytoprotective actions of resveratrol. Oxid. Med. Cell. Longev., 2015, 2015, 1-15.
[http://dx.doi.org/10.1155/2015/803971] [PMID: 26180596]
[169]
Jardim, F.R.; de Rossi, F.T.; Nascimento, M.X.; da Silva Barros, R.G.; Borges, P.A.; Prescilio, I.C.; de Oliveira, M.R. Resveratrol and brain mitochondria: A review. Mol. Neurobiol., 2018, 55(3), 2085-2101.
[http://dx.doi.org/10.1007/s12035-017-0448-z] [PMID: 28283884]
[170]
Wichur, T.; Pasieka, A. Godyń J.; Panek, D.; Góral, I.; Latacz, G.; Honkisz-Orzechowska, E.; Bucki, A.; Siwek, A.; Głuch-Lutwin, M.; Knez, D.; Brazzolotto, X.; Gobec, S.; Kołaczkowski, M.; Sabate, R.; Malawska, B.; Więckowska, A. Discovery of 1-(phenylsulfonyl)-1H-indole-based multifunctional ligands targeting cholinesterases and 5-HT6 receptor with anti-aggregation properties against amyloid-beta and tau. Eur. J. Med. Chem., 2021, 225, 113783.
[http://dx.doi.org/10.1016/j.ejmech.2021.113783] [PMID: 34461507]
[171]
Moussa, C.; Hebron, M.; Huang, X.; Ahn, J.; Rissman, R.A.; Aisen, P.S.; Turner, R.S. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer’s Disease. J. Neuroinflammation, 2017, 14(1), 1-10.
[http://dx.doi.org/10.1186/s12974-016-0779-0] [PMID: 28086917]
[172]
Schweiger, S.; Matthes, F.; Posey, K.; Kickstein, E.; Weber, S.; Hettich, M.M.; Pfurtscheller, S.; Ehninger, D.; Schneider, R.; Krauß, S. Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex. Sci. Rep., 2017, 7(1), 13753.
[http://dx.doi.org/10.1038/s41598-017-12974-4] [PMID: 29062069]
[173]
Corpas, R.; Griñán-Ferré, C.; Rodríguez-Farré, E.; Pallàs, M.; Sanfeliu, C. Resveratrol induces brain resilience against alzheimer neurodegeneration through proteostasis enhancement. Mol. Neurobiol., 2019, 56(2), 1502-1516.
[http://dx.doi.org/10.1007/s12035-018-1157-y] [PMID: 29948950]
[174]
Turner, R.S.; Thomas, R.G.; Craft, S.; van Dyck, C.H.; Mintzer, J.; Reynolds, B.A.; Brewer, J.B.; Rissman, R.A.; Raman, R.; Aisen, P.S. A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology, 2015, 85(16), 1383-1391.
[http://dx.doi.org/10.1212/WNL.0000000000002035] [PMID: 26362286]
[175]
Wu, L.; Sun, D.; He, Y. Coffee intake and the incident risk of cognitive disorders: A dose–response meta-analysis of nine prospective cohort studies. Clin. Nutr., 2017, 36(3), 730-736.
[http://dx.doi.org/10.1016/j.clnu.2016.05.015] [PMID: 27288328]
[176]
Santos, G.L.; Hartmann, S.; Zimmermann, W.H.; Ridley, A.; Lutz, S. Inhibition of Rho-associated kinases suppresses cardiac myofibroblast function in engineered connective and heart muscle tissues. J. Mol. Cell. Cardiol., 2019, 134(134), 13-28.
[http://dx.doi.org/10.1016/j.yjmcc.2019.06.015] [PMID: 31233754]
[177]
Kim, Y.S.; Kwak, S.M.; Myung, S.K. Caffeine intake from coffee or tea and cognitive disorders: A meta-analysis of observational studies. Neuroepidemiology, 2015, 44(1), 51-63.
[http://dx.doi.org/10.1159/000371710] [PMID: 25721193]
[178]
Reidel, W.; Hogervorst, E.; Leboux, R.; Verhey, F.; van Praag, H.; Jolles, J. Caffeine attenuates scopolamine-induced memory impairment in humans. Psychopharmacology, 1995, 122(2), 158-168.
[http://dx.doi.org/10.1007/BF02246090] [PMID: 8848531]
[179]
Cascella, M.; Bimonte, S.; Muzio, M.R.; Schiavone, V.; Cuomo, A. The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer’s disease: An overview of pre-clinical studies and translational perspectives in clinical practice. Infect. Agent. Cancer, 2017, 12(1), 36.
[http://dx.doi.org/10.1186/s13027-017-0145-6] [PMID: 28642806]
[180]
Jin, G.; Bai, D.; Yin, S.; Yang, Z.; Zou, D.; Zhang, Z.; Li, X.; Sun, Y.; Zhu, Q. Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice. Neurosci. Lett., 2016, 629, 256-261.
[http://dx.doi.org/10.1016/j.neulet.2016.06.008] [PMID: 27276653]
[181]
Hostetler, G.L.; Ralston, R.A.; Schwartz, S.J. Flavones  Food sources; Bioavailability, 2017, pp. 423-435.
[182]
Wu, L.; Tong, T.; Wan, S.; Yan, T.; Ren, F.; Bi, K.; Jia, Y. Protective effects of puerarin against Aβ 1-42-induced learning and memory impairments in mice. Planta Med., 2016, 83(03/04), 224-231.
[http://dx.doi.org/10.1055/s-0042-111521] [PMID: 27420352]
[183]
Dommels, Y. Effects of N-6 and n-3 polyunsaturated fatty acids on colorectal carcinogenesis. 2017, 9(1), 1-9.
[184]
Lo Verme, J.; Fu, J.; Astarita, G.; La Rana, G.; Russo, R.; Calignano, A.; Piomelli, D. The nuclear receptor peroxisome proliferator-activated receptor-α mediates the anti-inflammatory actions of palmitoylethanolamide. Mol. Pharmacol., 2005, 67(1), 15-19.
[http://dx.doi.org/10.1124/mol.104.006353] [PMID: 15465922]
[185]
Beggiato, S.; Tomasini, M.C.; Ferraro, L. Palmitoylethanolamide (PEA) as a potential therapeutic agent in alzheimer’s disease. Front. Pharmacol., 2019, 10(July), 821.
[http://dx.doi.org/10.3389/fphar.2019.00821] [PMID: 31396087]
[186]
Andrieu, S.; Guyonnet, S.; Coley, N.; Cantet, C.; Bonnefoy, M.; Bordes, S.; Bories, L.; Cufi, M.N.; Dantoine, T.; Dartigues, J.F.; Desclaux, F.; Gabelle, A.; Gasnier, Y.; Pesce, A.; Sudres, K.; Touchon, J.; Robert, P.; Rouaud, O.; Legrand, P.; Payoux, P.; Caubere, J.P.; Weiner, M.; Carrié, I.; Ousset, P.J.; Vellas, B.; Vellas, B.; Guyonnet, S.; Carrié, I.; Brigitte, L.; Faisant, C.; Lala, F.; Delrieu, J.; Villars, H.; Combrouze, E.; Badufle, C.; Zueras, A.; Andrieu, S.; Cantet, C.; Morin, C.; Van Kan, G.A.; Dupuy, C.; Rolland, Y.; Caillaud, C.; Ousset, P-J.; Fougère, B.; Willis, S.; Belleville, S.; Gilbert, B.; Fontaine, F.; Dartigues, J-F.; Marcet, I.; Delva, F.; Foubert, A.; Cerda, S.; Noëlle-Cuffi, M.; Costes, C.; Rouaud, O.; Manckoundia, P.; Quipourt, V.; Marilier, S.; Franon, E.; Bories, L.; Pader, M-L.; Basset, M-F.; Lapoujade, B.; Faure, V.; Li, M.; Tong, Y.; Malick-Loiseau, C.; Cazaban-Campistron, E.; Desclaux, F.; Blatge, C.; Dantoine, T.; Laubarie-Mouret, C.; Saulnier, I.; Clément, J-P.; Picat, M-A.; Bernard-Bourzeix, L.; Willebois, S.; Désormais, I.; Cardinaud, N.; Bonnefoy, M.; Livet, P.; Rebaudet, P.; Gédéon, C.; Burdet, C.; Terracol, F.; Pesce, A.; Roth, S.; Chaillou, S.; Louchart, S.; Sudres, K.; Lebrun, N.; Barro-Belaygues, N.; Touchon, J.; Bennys, K.; Gabelle, A.; Romano, A.; Touati, L.; Marelli, C.; Pays, C.; Robert, P.; Le Duff, F.; Gervais, C.; Gonfrier, S.; Gasnier, Y.; Bordes, S.; Begorre, D.; Carpuat, C.; Khales, K.; Lefebvre, J-F.; El Idrissi, S.M.; Skolil, P.; Salles, J-P.; Dufouil, C.; Lehéricy, S.; Chupin, M.; Mangin, J-F.; Bouhayia, A.; Allard, M.; Ricolfi, F.; Dubois, D.; Paule, M.; Martel, B.; Cotton, F.; Bonafé, A.; Chanalet, S.; Hugon, F.; Bonneville, F.; Cognard, C.; Chollet, F.; Payoux, P.; Voisin, T.; Peiffer, S.; Hitzel, A.; Allard, M.; Zanca, M.; Monteil, J.; Darcourt, J.; Molinier, L.; Derumeaux, H.; Costa, N.; Vincent, C.; Perret, B.; Vinel, C.; Olivier-Abbal, P. Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): A randomised, placebo-controlled trial. Lancet Neurol., 2017, 16(5), 377-389.
[http://dx.doi.org/10.1016/S1474-4422(17)30040-6] [PMID: 28359749]
[187]
Im, D.S. Pro-resolving effect of ginsenosides as an anti-inflammatory mechanism of Panax ginseng. Biomolecules, 2020, 10(3), 444.
[http://dx.doi.org/10.3390/biom10030444] [PMID: 32183094]
[188]
Du, Y.; Fu, M.; Wang, Y.T.; Dong, Z. Neuroprotective effects of ginsenoside rf on amyloid-β-induced neurotoxicity in vitro and in vivo. J. Alzheimers Dis., 2018, 64(1), 309-322.
[http://dx.doi.org/10.3233/JAD-180251] [PMID: 29865080]
[189]
Sachdeva, A.K.; Chopra, K. Lycopene abrogates Aβ(1–42)-mediated neuroinflammatory cascade in an experimental model of Alzheimer’s Disease. J. Nutr. Biochem., 2015, 26(7), 736-744.
[http://dx.doi.org/10.1016/j.jnutbio.2015.01.012] [PMID: 25869595]
[190]
von Arnim, C.A.F.; Herbolsheimer, F.; Nikolaus, T.; Peter, R.; Biesalski, H.K.; Ludolph, A.C.; Riepe, M.; Nagel, G. Dietary antioxidants and dementia in a population-based case-control study among older people in South Germany. J. Alzheimers Dis., 2012, 31(4), 717-724.
[http://dx.doi.org/10.3233/JAD-2012-120634] [PMID: 22710913]
[191]
Atkinson, F. S.; Villar, A.; Mul, A.; Zangara, A.; Risco, E.; Smidt, C. R.; Hontecillas, R.; Leber, A.; Bassaganya-riera, J. Responses in Healthy Adults. 2006, 1.
[192]
Khorasani, A.; Abbasnejad, M.; Esmaeili-Mahani, S. Phytohormone abscisic acid ameliorates cognitive impairments in streptozotocin-induced rat model of Alzheimer’s Disease through PPARβ/δ and PKA signaling. Int. J. Neurosci., 2019, 129(11), 1053-1065.
[http://dx.doi.org/10.1080/00207454.2019.1634067] [PMID: 31215291]
[193]
Sánchez-Sarasúa, S.; Moustafa, S.; García-Avilés, Á.; López-Climent, M.F.; Gómez-Cadenas, A.; Olucha-Bordonau, F.E.; Sánchez-Pérez, A.M. The effect of abscisic acid chronic treatment on neuroinflammatory markers and memory in a rat model of high-fat diet induced neuroinflammation. Nutr. Metab., 2016, 13(1), 73.
[http://dx.doi.org/10.1186/s12986-016-0137-3] [PMID: 27795733]
[194]
Ribes-Navarro, A.; Atef, M.; Sánchez-Sarasúa, S.; Beltrán-Bretones, M.T.; Olucha-Bordonau, F.; Sánchez-Pérez, A.M. Abscisic acid supplementation rescues high fat diet-induced alterations in hippocampal inflammation and irss expression. Mol. Neurobiol., 2019, 56(1), 454-464.
[http://dx.doi.org/10.1007/s12035-018-1091-z] [PMID: 29721854]
[195]
Espinosa-Fernández, V.; Mañas-Ojeda, A.; Pacheco-Herrero, M.; Castro-Salazar, E.; Ros-Bernal, F.; Sánchez-Pérez, A.M. Early intervention with ABA prevents neuroinflammation and memory impairment in a triple transgenic mice model of Alzheimer’s Disease. Behav. Brain Res., 2019, 374(June), 112106.
[http://dx.doi.org/10.1016/j.bbr.2019.112106] [PMID: 31356828]
[196]
Kan, L.; Smith, A.; Chen, M.; Ledford, B.T.; Fan, H. Rho-associated kinase inhibitor (Y-27632); Attenuates Doxorubicin-Induced Apoptosis of Human Cardiac Stem Cells, 2015, pp. 1-21.
[http://dx.doi.org/10.1371/journal.pone.0144513]
[197]
Heo, J.H.; Lee, S.T.; Chu, K.; Oh, M.J.; Park, H.J.; Shim, J.Y.; Kim, M. Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer’s disease. Nutr. Neurosci., 2012, 15(6), 278-282.
[http://dx.doi.org/10.1179/1476830512Y.0000000027] [PMID: 22780999]
[198]
Zou, K.; Abdullah, M.; Michikawa, M. Current biomarkers for Alzheimer’s disease: From CSF to Blood. J. Pers. Med., 2020, 10(3), 85.
[http://dx.doi.org/10.3390/jpm10030085] [PMID: 32806668]
[199]
Jain, S.; Chauhan, N.; Sharma, S.; Reddy, K.R.; Sadhu, V.; Kulkarni, R.V. The link between anxiety and Alzheimer’s disease: Critical facts; INC, 2020.
[http://dx.doi.org/10.1016/B978-0-12-817923-9.00012-2]
[200]
Watt, G.; Karl, T. In vivo Evidence for Therapeutic Properties of Cannabidiol (CBD) for Alzheimer’s Disease. Front. Pharmacol., 2017, 8(FEB), 20.
[http://dx.doi.org/10.3389/fphar.2017.00020] [PMID: 28217094]
[201]
Patel, S.; Shukla, J.; Jain, S.; Paliwal, V.; Tripathi, N.; Paliwal, S.; Sharma, S. Repositioning of tubocurarine as analgesic and anti-inflammatory agent: Exploring beyond myorelaxant activity. Biochem. Pharmacol., 2022, 205(May), 115248.
[http://dx.doi.org/10.1016/j.bcp.2022.115248] [PMID: 36113566]
[202]
Sharma, M.; Mittal, A.; Singh, A.; Jainarayanan, A.K.; Sharma, S.; Paliwal, S. Pharmacophore-driven identification of N-methyl-D-receptor antagonists as potent neuroprotective agents validated using in vivo studies. Biol. Methods Protoc., 2020, 5(1), bpaa013.
[http://dx.doi.org/10.1093/biomethods/bpaa013] [PMID: 32913897]
[203]
Outen, J.D.; Burhanullah, M.H.; Vandrey, R.; Amjad, H.; Harper, D.G.; Patrick, R.E.; May, R.L.; Agronin, M.E.; Forester, B.P.; Rosenberg, P.B. Cannabinoids for agitation in Alzheimer’s Disease. Am. J. Geriatr. Psychiatry, 2021, 29(12), 1253-1263.
[http://dx.doi.org/10.1016/j.jagp.2021.01.015] [PMID: 33573996]
[204]
Jain, S.; Chauhan, N.; Bhardwaj, A.; Yadaw, G.; Singh, M.K.; Mishra, A. QSAR Modeling of α-Ketooxazole Motif Analogues as Potent Anti-Alzheimer Agents. YMER Digital, 2022, 21(5), 624-640.
[http://dx.doi.org/10.37896/YMER21.05/71]
[205]
Bilkei-Gorzo, A.; Racz, I.; Valverde, O.; Otto, M.; Michel, K.; Sarstre, M.; Zimmer, A. Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors. Proc. Natl. Acad. Sci., 2005, 102(43), 15670-15675.
[http://dx.doi.org/10.1073/pnas.0504640102] [PMID: 16221768]
[206]
Ramírez, B.G.; Blázquez, C.; Gómez del Pulgar, T.; Guzmán, M.; de Ceballos, M.L. Prevention of Alzheimer’s Disease pathology by cannabinoids: Neuroprotection mediated by blockade of microglial activation. J. Neurosci., 2005, 25(8), 1904-1913.
[http://dx.doi.org/10.1523/JNEUROSCI.4540-04.2005] [PMID: 15728830]
[207]
Gorey, C.; Kuhns, L.; Smaragdi, E.; Kroon, E.; Cousijn, J. Age-related differences in the impact of cannabis use on the brain and cognition: A systematic review. Eur. Arch. Psychiatry Clin. Neurosci., 2019, 269(1), 37-58.
[http://dx.doi.org/10.1007/s00406-019-00981-7] [PMID: 30680487]
[208]
Rouyer, O.; Geny, B. Evolocumab in hyperlipidemia. N. Engl. J. Med., 2014, 371(9), 876-878.
[http://dx.doi.org/10.1056/NEJMc1408237]
[209]
Patel, S.; Gururani, R.; Jain, S.; Tripathi, N.; Paliwal, S.; Paliwal, S.; Paliwal, S.; Sharma, S. Repurposing of digoxin in pain and inflammation: An evidence‐based study. Drug Dev. Res., 2022, 83(5), 1097-1110.
[http://dx.doi.org/10.1002/ddr.21935] [PMID: 35315525]
[210]
Cassano, T.; Calcagnini, S.; Pace, L.; De Marco, F.; Romano, A.; Gaetani, S. Cannabinoid receptor 2 signaling in neurodegenerative disorders: From pathogenesis to a promising therapeutic target. Front. Neurosci., 2017, 11(FEB), 30.
[http://dx.doi.org/10.3389/fnins.2017.00030] [PMID: 28210207]
[211]
Kendall, D.A.; Yudowski, G.A. Cannabinoid receptors in the central nervous system: Their signaling and roles in disease. Front. Cell. Neurosci., 2017, 10, 294.
[http://dx.doi.org/10.3389/fncel.2016.00294] [PMID: 28101004]
[212]
Tolón, R.M.; Núñez, E.; Pazos, M.R.; Benito, C.; Castillo, A.I.; Martínez-Orgado, J.A.; Romero, J. The activation of cannabinoid CB2 receptors stimulates in situ and in vitro beta-amyloid removal by human macrophages. Brain Res., 2009, 1283, 148-154.
[http://dx.doi.org/10.1016/j.brainres.2009.05.098] [PMID: 19505450]
[213]
Solas, M.; Francis, P.T.; Franco, R.; Ramirez, M.J. CB2 receptor and amyloid pathology in frontal cortex of Alzheimer’s disease patients. Neurobiol. Aging, 2013, 34(3), 805-808.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.06.005] [PMID: 22763024]
[214]
Tak, K.; Sharma, P.; Sharma, R.; Dave, V.; Jain, S.; Sharma, S. One-pot hydrothermal green synthesis of Polygala tenuifolia mediated graphene quantum dots for acetylcholine esterase inhibitory activity. J. Drug Deliv. Sci. Technol., 2022, 73, 103486.
[http://dx.doi.org/10.1016/j.jddst.2022.103486]
[215]
Aso, E.; Juvés, S.; Maldonado, R.; Ferrer, I. CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AβPP/PS1 mice. J. Alzheimers Dis., 2013, 35(4), 847-858.
[http://dx.doi.org/10.3233/JAD-130137] [PMID: 23515018]
[216]
Amandine, E.B.; Yannick, M. Potential therapeutical contributions of the endocannabinoid system towards aging and Alzheimer’s Disease. Aging Dis., 2015, 6(5), 400-405.
[http://dx.doi.org/10.14336/AD.2015.0617] [PMID: 26425394]
[217]
Cassano, T.; Villani, R.; Pace, L.; Carbone, A.; Bukke, V.N.; Orkisz, S.; Avolio, C.; Serviddio, G. From Cannabis sativa to Cannabidiol: Promising therapeutic candidate for the treatment of neurodegenerative diseases. Front. Pharmacol., 2020, 11, 124.
[http://dx.doi.org/10.3389/fphar.2020.00124] [PMID: 32210795]
[218]
Pihlaja, R.; Takkinen, J.; Eskola, O.; Vasara, J.; López-Picón, F.R.; Haaparanta-Solin, M.; Rinne, J.O. Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells. J. Neuroinflammation, 2015, 12(1), 81.
[http://dx.doi.org/10.1186/s12974-015-0305-9] [PMID: 25927213]
[219]
Woelfl, T.; Rohleder, C.; Mueller, J.K.; Lange, B.; Reuter, A.; Schmidt, A.M.; Koethe, D.; Hellmich, M.; Leweke, F.M. Effects of cannabidiol and delta-9-tetrahydrocannabinol on emotion, cognition, and attention: A double-blind, placebo-controlled, randomized experimental trial in healthy volunteers. Front. Psychiatry, 2020, 11(11), 576877.
[http://dx.doi.org/10.3389/fpsyt.2020.576877] [PMID: 33304282]
[220]
Tak, K.; Sharma, R.; Dave, V.; Jain, S.; Sharma, S. Clitoria ternatea Mediated Synthesis of Graphene Quantum Dots for the Treatment of Alzheimer’s Disease. ACS Chem. Neurosci., 2020, 11(22), 3741-3748.
[http://dx.doi.org/10.1021/acschemneuro.0c00273] [PMID: 33119989]
[221]
Pertwee, R.G. The diverse CB 1 and CB 2 receptor pharmacology of three plant cannabinoids: Δ 9 -tetrahydrocannabinol, cannabidiol and Δ 9 -tetrahydrocannabivarin. Br. J. Pharmacol., 2008, 153(2), 199-215.
[http://dx.doi.org/10.1038/sj.bjp.0707442] [PMID: 17828291]
[222]
Chung, H.; Fierro, A.; Pessoa-Mahana, C.D. Cannabidiol binding and negative allosteric modulation at the cannabinoid type 1 receptor in the presence of delta-9-tetrahydrocannabinol: An in silico study. PLoS One, 2019, 14(7), e0220025.
[http://dx.doi.org/10.1371/journal.pone.0220025] [PMID: 31335889]
[223]
Laprairie, R.B.; Bagher, A.M.; Kelly, M.E.M.; Denovan-Wright, E.M. Cannabidiol is a negative allosteric modulator of the cannabinoid CB 1 receptor. Br. J. Pharmacol., 2015, 172(20), 4790-4805.
[http://dx.doi.org/10.1111/bph.13250] [PMID: 26218440]
[224]
Tham, M.; Yilmaz, O.; Alaverdashvili, M.; Kelly, M.E.M.; Denovan-Wright, E.M.; Laprairie, R.B. Allosteric and orthosteric pharmacology of cannabidiol and cannabidiol-dimethylheptyl at the type 1 and type 2 cannabinoid receptors. Br. J. Pharmacol., 2019, 176(10), 1455-1469.
[http://dx.doi.org/10.1111/bph.14440] [PMID: 29981240]
[225]
Scuderi, C.; Steardo, L.; Esposito, G. Cannabidiol promotes amyloid precursor protein ubiquitination and reduction of beta amyloid expression in SHSY5YAPP+ cells through PPARγ involvement. Phytother. Res., 2014, 28(7), 1007-1013.
[http://dx.doi.org/10.1002/ptr.5095] [PMID: 24288245]
[226]
Janefjord, E.; Mååg, J.L.V.; Harvey, B.S.; Smid, S.D. Cannabinoid effects on β amyloid fibril and aggregate formation, neuronal and microglial-activated neurotoxicity in vitro. Cell. Mol. Neurobiol., 2014, 34(1), 31-42.
[http://dx.doi.org/10.1007/s10571-013-9984-x] [PMID: 24030360]
[227]
Cheng, D.; Spiro, A.S.; Jenner, A.M.; Garner, B.; Karl, T. Long-term cannabidiol treatment prevents the development of social recognition memory deficits in Alzheimer’s disease transgenic mice. J. Alzheimers Dis., 2014, 42(4), 1383-1396.
[http://dx.doi.org/10.3233/JAD-140921] [PMID: 25024347]
[228]
Thompson, K.J.; Tobin, A.B. Crosstalk between the M1 muscarinic acetylcholine receptor and the endocannabinoid system: A relevance for Alzheimer’s disease? Cell. Signal., 2020, 70(1), 109545.
[http://dx.doi.org/10.1016/j.cellsig.2020.109545] [PMID: 31978506]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy