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Current Neuropharmacology

Editor-in-Chief

ISSN (Print): 1570-159X
ISSN (Online): 1875-6190

Review Article

Current and Near-Future Treatment of Alzheimer’s Disease

Author(s): Kazimierz Gąsiorowski, Jadwiga Barbara Brokos, Marta Sochocka, Michał Ochnik, Justyna Chojdak-Łukasiewicz, Katarzyna Zajączkowska, Michał Fułek and Jerzy Leszek*

Volume 20, Issue 6, 2022

Published on: 23 December, 2021

Page: [1144 - 1157] Pages: 14

DOI: 10.2174/1570159X19666211202124239

open access plus

Abstract

Recent findings have improved our understanding of the multifactorial nature of AD. While in early asymptomatic stages of AD, increased amyloid-β synthesis and tau hyperphosphorylation play a key role, while in the latter stages of the disease, numerous dysfunctions of homeostatic mechanisms in neurons, glial cells, and cerebrovascular endothelium determine the rate of progression of clinical symptoms. The main driving forces of advanced neurodegeneration include increased inflammatory reactions in neurons and glial cells, oxidative stress, deficiencies in neurotrophic growth and regenerative capacity of neurons, brain insulin resistance with disturbed metabolism in neurons, or reduction of the activity of the Wnt-β catenin pathway, which should integrate the homeostatic mechanisms of brain tissue. In order to more effectively inhibit the progress of neurodegeneration, combination therapies consisting of drugs that rectify several above-mentioned dysfunctions should be used. It should be noted that many widely-used drugs from various pharmacological groups, "in addition" to the main therapeutic indications, have a beneficial effect on neurodegeneration and may be introduced into clinical practice in combination therapy of AD. There is hope that complex treatment will effectively inhibit the progression of AD and turn it into a slowly progressing chronic disease. Moreover, as the mechanisms of bidirectional communication between the brain and microbiota are better understood, it is expected that these pathways will be harnessed to provide novel methods to enhance health and treat AD.

Keywords: Alzheimer’s disease, inflammation, oxidative stress, Wnt-β catenin pathway, combination therapy, brain insulin resistance.

Graphical Abstract

[1]
2017 Alzheimer’s Disease Facts and Figures. Alzheimers Dement., 2017, 13(4), 325-373.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[2]
World Health Organization. Dementia. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia (accessed April 13, 2021).
[3]
Du, X.; Wang, X.; Geng, M. Alzheimer’s disease hypothesis and related therapies. Transl. Neurodegener., 2018, 7, 2.
[http://dx.doi.org/10.1186/s40035-018-0107-y] [PMID: 29423193]
[4]
Mendiola-Precoma, J.; Berumen, L.C.; Padilla, K.; Garcia-Alcocer, G. Therapies for prevention and treatment of Alzheimer’s disease. BioMed Res. Int., 2016, 2016, 2589276.
[http://dx.doi.org/10.1155/2016/2589276] [PMID: 27547756]
[5]
Stephenson, D.; Perry, D.; Bens, C.; Bain, L.J.; Berry, D.; Krams, M.; Sperling, R.; Dilts, D.; Luthman, J.; Hanna, D.; McKew, J.; Temple, R.; Fields, F.O.; Salloway, S.; Katz, R. Charting a path toward combination therapy for Alzheimer’s disease. Expert Rev. Neurother., 2015, 15(1), 107-113.
[http://dx.doi.org/10.1586/14737175.2015.995168] [PMID: 25540951]
[6]
Bredesen, D.E.; John, V. Next generation therapeutics for Alzheimer’s disease. EMBO Mol. Med., 2013, 5(6), 795-798.
[http://dx.doi.org/10.1002/emmm.201202307] [PMID: 23703924]
[7]
Musiek, E.S.; Holtzman, D.M. Three dimensions of the amyloid hypothesis: Time, space and ‘wingmen’. Nat. Neurosci., 2015, 18(6), 800-806.
[http://dx.doi.org/10.1038/nn.4018] [PMID: 26007213]
[8]
Bredesen, D.E. Reversal of cognitive decline: A novel therapeutic program. Aging (Albany NY), 2014, 6(9), 707-717.
[http://dx.doi.org/10.18632/aging.100690] [PMID: 25324467]
[9]
Kametani, F.; Hasegawa, M. Reconsideration of amyloid hypothesis and tau hypothesis in Alzheimer’s disease. Front. Neurosci., 2018, 12, 25.
[http://dx.doi.org/10.3389/fnins.2018.00025] [PMID: 29440986]
[10]
Godyń, J.; Jończyk, J.; Panek, D.; Malawska, B. Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol. Rep., 2016, 68(1), 127-138.
[http://dx.doi.org/10.1016/j.pharep.2015.07.006] [PMID: 26721364]
[11]
Pakavathkumar, P.; Sharma, G.; Kaushal, V.; Foveau, B.; LeBlanc, A.C. Methylene blue inhibits caspases by oxidation of the catalytic cysteine. Sci. Rep., 2015, 5, 13730.
[http://dx.doi.org/10.1038/srep13730] [PMID: 26400108]
[12]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[13]
Obulesu, M.; Lakshmi, M.J. Apoptosis in Alzheimer’s disease: An understanding of the physiology, pathology and therapeutic avenues. Neurochem. Res., 2014, 39(12), 2301-2312.
[http://dx.doi.org/10.1007/s11064-014-1454-4] [PMID: 25322820]
[14]
Miller, D.R.; Cramer, S.D.; Thorburn, A. The Interplay of Autophagy and Non-Apoptotic Cell Death Pathways. In:International Review of Cell and Molecular Biology; Spetz, J. K.E.; Galluzzi, L. Academic Press, 2020; 353, pp. 159-187.
[15]
Zhen, X.; Zhao, G. Pyroptosis and neurological diseases. Neuroimmunol. Neuroinflamm., 2014, 1, 60-65.
[http://dx.doi.org/10.4103/2347-8659.139716]
[16]
Han, C.; Yang, Y.; Guan, Q.; Zhang, X.; Shen, H.; Sheng, Y.; Wang, J.; Zhou, X.; Li, W.; Guo, L.; Jiao, Q. New mechanism of nerve injury in Alzheimer’s disease: β-amyloid-induced neuronal pyroptosis. J. Cell. Mol. Med., 2020, 24(14), 8078-8090.
[http://dx.doi.org/10.1111/jcmm.15439] [PMID: 32521573]
[17]
David, K.K.; Andrabi, S.A.; Dawson, T.M.; Dawson, V.L. Parthanatos, a messenger of death. Front. Biosci., 2009, 14, 1116-1128.
[http://dx.doi.org/10.2741/3297] [PMID: 19273119]
[18]
Wang, X.; Ge, P. Parthanatos in the pathogenesis of nervous system diseases. Neuroscience, 2020, 449, 241-250.
[http://dx.doi.org/10.1016/j.neuroscience.2020.09.049] [PMID: 33039521]
[19]
Weerasinghe, P.; Buja, L.M. Oncosis: An important non-apoptotic mode of cell death. Exp. Mol. Pathol., 2012, 93(3), 302-308.
[http://dx.doi.org/10.1016/j.yexmp.2012.09.018] [PMID: 23036471]
[20]
Nirmala, J.G.; Lopus, M. Cell death mechanisms in eukaryotes. Cell Biol. Toxicol., 2020, 36(2), 145-164.
[http://dx.doi.org/10.1007/s10565-019-09496-2] [PMID: 31820165]
[21]
Hikari, T.; Homma, H.; Fujita, K.; Kondo, K.; Yamada, S.; Jin, X.; Waragai, M.; Ohtomo, G.; Iwata, A.; Tagawa, K.; Atsuta, N.; Katsuno, M.; Tomita, N.; Furukawa, K.; Saito, Y.; Saito, T.; Ichise, A.; Shibata, S.; Arai, H.; Saido, T.; Sudol, M.; Muramatsu, S.; Okano, H.; Mufson, E.J.; Sobue, G.; Murayama, S.; Okazawa, H. YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology. Nat. Commun., 2020, 11(1), 1-22.
[PMID: 31911652]
[22]
Callus, B.A.; Vaux, D.L. Caspase inhibitors: viral, cellular and chemical. Cell Death Differ., 2007, 14(1), 73-78.
[http://dx.doi.org/10.1038/sj.cdd.4402034] [PMID: 16946729]
[23]
Caccamo, A.; Branca, C.; Piras, I.S.; Ferreira, E.; Huentelman, M.J.; Liang, W.S.; Readhead, B.; Dudley, J.T.; Spangenberg, E.E.; Green, K.N.; Belfiore, R.; Winslow, W.; Oddo, S. Necroptosis activation in Alzheimer’s disease. Nat. Neurosci., 2017, 20(9), 1236-1246.
[http://dx.doi.org/10.1038/nn.4608] [PMID: 28758999]
[24]
Leszek, J.; Trypka, E.; Tarasov, V.V.; Ashraf, G.M.; Aliev, G. Type 3 diabetes mellitus: A novel implication of Alzheimers disease. Curr. Top. Med. Chem., 2017, 17(12), 1331-1335.
[http://dx.doi.org/10.2174/1568026617666170103163403] [PMID: 28049395]
[25]
Ferreira, L.S.S.; Fernandes, C.S.; Vieira, M.N.N.; De Felice, F.G. Insulin resistance in Alzheimer’s disease. Front. Neurosci., 2018, 12, 830.
[http://dx.doi.org/10.3389/fnins.2018.00830] [PMID: 30542257]
[26]
Kim, B.; Feldman, E.L. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome. Exp. Mol. Med., 2015, 47, e149.
[http://dx.doi.org/10.1038/emm.2015.3] [PMID: 25766618]
[27]
Accardi, G.; Caruso, C.; Colonna-Romano, G.; Camarda, C.; Monastero, R.; Candore, G. Can Alzheimer disease be a form of type 3 diabetes? Rejuvenation Res., 2012, 15(2), 217-221.
[http://dx.doi.org/10.1089/rej.2011.1289] [PMID: 22533436]
[28]
Fernando, W.M.D.B.; Martins, I.J.; Goozee, K.G.; Brennan, C.S.; Jayasena, V.; Martins, R.N. The role of dietary coconut for the prevention and treatment of Alzheimer’s disease: Potential mechanisms of action. Br. J. Nutr., 2015, 114(1), 1-14.
[http://dx.doi.org/10.1017/S0007114515001452] [PMID: 25997382]
[29]
Kosik, K.S. Personalized medicine for effective Alzheimer disease treatment. JAMA Neurol., 2015, 72(5), 497-498.
[http://dx.doi.org/10.1001/jamaneurol.2014.3445] [PMID: 25730751]
[30]
Gao, C.; Ding, Y.; Zhong, L.; Jiang, L.; Geng, C.; Yao, X.; Cao, J. Tacrine induces apoptosis through lysosome- and mitochondria-dependent pathway in HepG2 cells. Toxicol. Vitro Int. J. Publ. Assoc. BIBRA, 2014, 28(4), 667-674.
[http://dx.doi.org/10.1016/j.tiv.2014.02.001] [PMID: 24560791]
[31]
Minarini, A.; Milelli, A.; Simoni, E.; Rosini, M.; Bolognesi, M.L.; Marchetti, C.; Tumiatti, V. Multifunctional tacrine derivatives in Alzheimer’s disease. Curr. Top. Med. Chem., 2013, 13(15), 1771-1786.
[http://dx.doi.org/10.2174/15680266113139990136] [PMID: 23931443]
[32]
Campos, C.; Rocha, N.B.; Vieira, R.T.; Rocha, S.A.; Telles-Correia, D.; Paes, F.; Yuan, T.; Nardi, A.E.; Arias-Carrión, O.; Machado, S.; Caixeta, L. Treatment of Cognitive Deficits in Alzheimer’s disease: A psychopharmacological review. Psychiatr. Danub., 2016, 28(1), 2-12.
[PMID: 26938815]
[33]
Sharma, K. Cholinesterase inhibitors as Alzheimer’s therapeutics (Review). Mol. Med. Rep., 2019, 20(2), 1479-1487.
[PMID: 31257471]
[34]
Molino, I.; Colucci, L.; Fasanaro, A.M.; Traini, E.; Amenta, F. Efficacy of memantine, donepezil, or their association in moderate-severe Alzheimer’s disease: A review of clinical trials. Scientific World J., 2013, 2013, 925702.
[http://dx.doi.org/10.1155/2013/925702] [PMID: 24288512]
[35]
Farrimond, L.E.; Roberts, E.; McShane, R. Memantine and cholinesterase inhibitor combination therapy for Alzheimer’s disease: A systematic review. BMJ Open, 2012, 2(3), e000917.
[http://dx.doi.org/10.1136/bmjopen-2012-000917] [PMID: 22689908]
[36]
Usman, M.B.; Bhardwaj, S.; Roychoudhury, S.; Kumar, D.; Alexiou, A.; Kumar, P.; Ambasta, R.K.; Prasher, P.; Shukla, S.; Upadhye, V.; Khan, F.A.; Awasthi, R.; Shastri, M.D.; Singh, S.K.; Gupta, G.; Chellappan, D.K.; Dua, K.; Jha, S.K.; Ruokolainen, J.; Kesari, K.K.; Ojha, S.; Jha, N.K. Immunotherapy for Alzheimer’s disease: current scenario and future perspectives. J. Prev. Alzheimers Dis., 2021, 8(4), 534-551.
[PMID: 34585229]
[37]
Mullard, A. FDA approval for Biogen’s aducanumab sparks Alzheimer’s disease firestorm. Nat. Rev. Drug Discov., 2021.
[38]
Jeremic, D.; Jiménez-Díaz, L.; Navarro-López, J.D. Past, present and future of therapeutic strategies against amyloid-β peptides in Alzheimer’s disease: A systematic review. Ageing Res. Rev., 2021, 72, 101496.
[http://dx.doi.org/10.1016/j.arr.2021.101496] [PMID: 34687956]
[39]
Selkoe, D.J. Alzheimer’s drugs: Does reducing amyloid work?-Response. Science, 2021, 374(6567), 545-546.
[http://dx.doi.org/10.1126/science.abm3288] [PMID: 34709920]
[40]
Sydow, A.; Hochgräfe, K.; Könen, S.; Cadinu, D.; Matenia, D.; Petrova, O.; Joseph, M.; Dennissen, F.J.; Mandelkow, E-M. Age-dependent neuroinflammation and cognitive decline in a novel Ala152Thr-Tau transgenic mouse model of PSP and AD. Acta Neuropathol. Commun., 2016, 4, 17.
[http://dx.doi.org/10.1186/s40478-016-0281-z] [PMID: 26916334]
[41]
Huang, W-J.; Zhang, X.; Chen, W-W. Role of oxidative stress in Alzheimer’s disease. Biomed. Rep., 2016, 4(5), 519-522.
[http://dx.doi.org/10.3892/br.2016.630] [PMID: 27123241]
[42]
Otaegui-Arrazola, A.; Amiano, P.; Elbusto, A.; Urdaneta, E.; Martínez-Lage, P. Diet, cognition, and Alzheimer’s disease: Food for thought. Eur. J. Nutr., 2014, 53(1), 1-23.
[http://dx.doi.org/10.1007/s00394-013-0561-3] [PMID: 23892520]
[43]
Szczechowiak, K.; Diniz, B.S.; Leszek, J. Diet and Alzheimer’s dementia - Nutritional approach to modulate inflammation. Pharmacol. Biochem. Behav., 2019, 184, 172743.
[http://dx.doi.org/10.1016/j.pbb.2019.172743] [PMID: 31356838]
[44]
Yang, G.; Wang, Y.; Sun, J.; Zhang, K.; Liu, J. Ginkgo biloba for mild cognitive impairment and Alzheimer’s disease: A systematic review and meta-analysis of randomized controlled trials. Curr. Top. Med. Chem., 2016, 16(5), 520-528.
[http://dx.doi.org/10.2174/1568026615666150813143520] [PMID: 26268332]
[45]
Lardenoije, R.; Iatrou, A.; Kenis, G.; Kompotis, K.; Steinbusch, H.W.M.; Mastroeni, D.; Coleman, P.; Lemere, C.A.; Hof, P.R.; van den Hove, D.L.A.; Rutten, B.P.F. The epigenetics of aging and neurodegeneration. Prog. Neurobiol., 2015, 131, 21-64.
[http://dx.doi.org/10.1016/j.pneurobio.2015.05.002] [PMID: 26072273]
[46]
Hardy, J.; Escott-Price, V. Genes, pathways and risk prediction in Alzheimer’s disease. Hum. Mol. Genet., 2019, 28(R2), R235-R240.
[http://dx.doi.org/10.1093/hmg/ddz163] [PMID: 31332445]
[47]
Sochocka, M.; Diniz, B.S.; Leszek, J. Inflammatory Response in the CNS: Friend or Foe? Mol. Neurobiol., 2017, 54(10), 8071-8089.
[http://dx.doi.org/10.1007/s12035-016-0297-1] [PMID: 27889895]
[48]
Gadhave, K.; Kumar, D.; Uversky, V.N.; Giri, R. A Multitude of signaling pathways associated with Alzheimer’s disease and their roles in AD pathogenesis and therapy. Med. Res. Rev., 2021, 41(5), 2689-2745.
[49]
Umeda, T.; Ono, K.; Sakai, A.; Yamashita, M.; Mizuguchi, M.; Klein, W.L.; Yamada, M.; Mori, H.; Tomiyama, T. Rifampicin is a candidate preventive medicine against amyloid-β and tau oligomers. Brain, 2016, 139(Pt 5), 1568-1586.
[http://dx.doi.org/10.1093/brain/aww042] [PMID: 27020329]
[50]
Nazir, M.A. Prevalence of periodontal disease, its association with systemic diseases and prevention. Int. J. Health Sci. (Qassim), 2017, 11(2), 72-80.
[PMID: 28539867]
[51]
Iizuka, T.; Morimoto, K.; Sasaki, Y.; Kameyama, M.; Kurashima, A.; Hayasaka, K.; Ogata, H.; Goto, H. Preventive effect of rifampicin on Alzheimer disease needs at least 450 mg daily for 1 year: An FDG-PET follow-up study. Dement. Geriatr. Cogn. Disord. Extra, 2017, 7(2), 204-214.
[http://dx.doi.org/10.1159/000477343] [PMID: 28690634]
[52]
Cummings, J.L.; Tong, G.; Ballard, C. Treatment combinations for Alzheimer’s disease: Current and future pharmacotherapy options. J. Alzheimers Dis., 2019, 67(3), 779-794.
[http://dx.doi.org/10.3233/JAD-180766] [PMID: 30689575]
[53]
Youdim, M.B.; Weinstock, M. Molecular basis of neuroprotective activities of rasagiline and the anti-Alzheimer drug TV3326 (N-propargyl-(3R)aminoindan-5-YL)-ethyl methyl carbamate. Cell. Mol. Neurobiol., 2001, 21(6), 555-573.
[http://dx.doi.org/10.1023/A:1015131516649] [PMID: 12043833]
[54]
Youdim, M.B.H.; Bar Am, O.; Yogev-Falach, M.; Weinreb, O.; Maruyama, W.; Naoi, M.; Amit, T. Rasagiline: Neurodegeneration, neuroprotection, and mitochondrial permeability transition. J. Neurosci. Res., 2005, 79(1-2), 172-179.
[http://dx.doi.org/10.1002/jnr.20350] [PMID: 15573406]
[55]
Matthews, D.C.; Ritter, A.; Thomas, R.G.; Andrews, R.D.; Lukic, A.S.; Revta, C.; Kinney, J.W.; Tousi, B.; Leverenz, J.B.; Fillit, H.; Zhong, K.; Feldman, H.H.; Cummings, J. Rasagiline effects on glucose metabolism, cognition, and tau in Alzheimer’s dementia. Alzheimers Dement. (N. Y.), 2021, 7(1), e12106.
[http://dx.doi.org/10.1002/trc2.12106] [PMID: 33614888]
[56]
Liberman, A.C.; Trias, E.; da Silva Chagas, L.; Trindade, P.; Dos Santos Pereira, M.; Refojo, D.; Hedin-Pereira, C.; Serfaty, C.A. Neuroimmune and inflammatory signals in complex disorders of the central nervous system. Neuroimmunomodulation, 2018, 25(5-6), 246-270.
[http://dx.doi.org/10.1159/000494761] [PMID: 30517945]
[57]
Ownby, R.L. Neuroinflammation and cognitive aging. Curr. Psychiatry Rep., 2010, 12(1), 39-45.
[http://dx.doi.org/10.1007/s11920-009-0082-1] [PMID: 20425309]
[58]
Jaturapatporn, D.; Isaac, M.G.E.K.N.; McCleery, J.; Tabet, N. Aspirin, steroidal and non-steroidal anti-inflammatory drugs for the treatment of Alzheimer’s disease. Cochrane Database Syst. Rev., 2012, (2), CD006378.
[http://dx.doi.org/10.1002/14651858.CD006378.pub2] [PMID: 22336816]
[59]
Miguel-Álvarez, M.; Santos-Lozano, A.; Sanchis-Gomar, F.; Fiuza-Luces, C.; Pareja-Galeano, H.; Garatachea, N.; Lucia, A. Non-steroidal anti-inflammatory drugs as a treatment for Alzheimer’s disease: A systematic review and meta-analysis of treatment effect. Drugs Aging, 2015, 32(2), 139-147.
[http://dx.doi.org/10.1007/s40266-015-0239-z] [PMID: 25644018]
[60]
Meyer, P-F.; Tremblay-Mercier, J.; Leoutsakos, J.; Madjar, C.; Lafaille-Maignan, M-É.; Savard, M.; Rosa-Neto, P.; Poirier, J.; Etienne, P.; Breitner, J. INTREPAD: A randomized trial of naproxen to slow progress of presymptomatic Alzheimer disease. Neurology, 2019, 92(18), e2070-e2080.
[http://dx.doi.org/10.1212/WNL.0000000000007232] [PMID: 30952794]
[61]
Aktas, O.; Ullrich, O.; Infante-Duarte, C.; Nitsch, R.; Zipp, F. Neuronal damage in brain inflammation. Arch. Neurol., 2007, 64(2), 185-189.
[http://dx.doi.org/10.1001/archneur.64.2.185] [PMID: 17296833]
[62]
Wyss-Coray, T.; Rogers, J. Inflammation in Alzheimer disease-a brief review of the basic science and clinical literature. Cold Spring Harb. Perspect. Med., 2012, 2(1), a006346.
[http://dx.doi.org/10.1101/cshperspect.a006346] [PMID: 22315714]
[63]
Dong, H.; Zhang, X.; Qian, Y. Mast cells and neuroinflammation. Med. Sci. Monit. Basic Res., 2014, 20, 200-206.
[http://dx.doi.org/10.12659/MSMBR.893093] [PMID: 25529562]
[64]
Shaik-Dasthagirisaheb, Y.B.; Conti, P. The role of mast cells in Alzheimer’s disease. Adv. Clin. Exp. Med., 2016, 25(4), 781-787.
[http://dx.doi.org/10.17219/acem/61914] [PMID: 27629855]
[65]
Piette, F.; Belmin, J.; Vincent, H.; Schmidt, N.; Pariel, S.; Verny, M.; Marquis, C.; Mely, J.; Hugonot-Diener, L.; Kinet, J-P.; Dubreuil, P.; Moussy, A.; Hermine, O. Masitinib as an adjunct therapy for mild-to-moderate Alzheimer’s disease: A randomised, placebo-controlled phase 2 trial. Alzheimers Res. Ther., 2011, 3(2), 16.
[http://dx.doi.org/10.1186/alzrt75] [PMID: 21504563]
[66]
Folch, J.; Petrov, D.; Ettcheto, M.; Pedrós, I.; Abad, S.; Beas-Zarate, C.; Lazarowski, A.; Marin, M.; Olloquequi, J.; Auladell, C.; Camins, A. Masitinib for the treatment of mild to moderate Alzheimer’s disease. Expert Rev. Neurother., 2015, 15(6), 587-596.
[http://dx.doi.org/10.1586/14737175.2015.1045419] [PMID: 25961655]
[67]
Chen, Y.; Zhou, K.; Wang, R.; Liu, Y.; Kwak, Y-D.; Ma, T.; Thompson, R.C.; Zhao, Y.; Smith, L.; Gasparini, L.; Luo, Z.; Xu, H.; Liao, F.F. Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer’s amyloid peptides via up-regulating BACE1 transcription. Proc. Natl. Acad. Sci. USA, 2009, 106(10), 3907-3912.
[http://dx.doi.org/10.1073/pnas.0807991106] [PMID: 19237574]
[68]
Beeri, M.S.; Schmeidler, J.; Silverman, J.M.; Gandy, S.; Wysocki, M.; Hannigan, C.M.; Purohit, D.P.; Lesser, G.; Grossman, H.T.; Haroutunian, V. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology, 2008, 71(10), 750-757.
[http://dx.doi.org/10.1212/01.wnl.0000324925.95210.6d] [PMID: 18765651]
[69]
Pedersen, W.A.; McMillan, P.J.; Kulstad, J.J.; Leverenz, J.B.; Craft, S.; Haynatzki, G.R. Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp. Neurol., 2006, 199(2), 265-273.
[http://dx.doi.org/10.1016/j.expneurol.2006.01.018] [PMID: 16515786]
[70]
Wang, R.; Li, J.J.; Diao, S.; Kwak, Y-D.; Liu, L.; Zhi, L.; Büeler, H.; Bhat, N.R.; Williams, R.W.; Park, E.A.; Liao, F.F. Metabolic stress modulates Alzheimer’s β-secretase gene transcription via SIRT1-PPARγ-PGC-1 in neurons. Cell Metab., 2013, 17(5), 685-694.
[http://dx.doi.org/10.1016/j.cmet.2013.03.016] [PMID: 23663737]
[71]
Freiherr, J.; Hallschmid, M.; Frey, W.H., II; Brünner, Y.F.; Chapman, C.D.; Hölscher, C.; Craft, S.; De Felice, F.G.; Benedict, C. Intranasal insulin as a treatment for Alzheimer’s disease: A review of basic research and clinical evidence. CNS Drugs, 2013, 27(7), 505-514.
[http://dx.doi.org/10.1007/s40263-013-0076-8] [PMID: 23719722]
[72]
Benedict, C.; Grillo, C.A. Insulin resistance as a therapeutic target in the treatment of Alzheimer’s disease: A state-of-the-art review. Front. Neurosci., 2018, 12, 215.
[http://dx.doi.org/10.3389/fnins.2018.00215] [PMID: 29743868]
[73]
Novak, V.; Milberg, W.; Hao, Y.; Munshi, M.; Novak, P.; Galica, A.; Manor, B.; Roberson, P.; Craft, S.; Abduljalil, A. Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes. Diabetes Care, 2014, 37(3), 751-759.
[http://dx.doi.org/10.2337/dc13-1672] [PMID: 24101698]
[74]
Mullins, R.J.; Diehl, T.C.; Chia, C.W.; Kapogiannis, D. Insulin resistance as a link between amyloid-beta and tau pathologies in Alzheimer’s disease. Front. Aging Neurosci., 2017, 9, 118.
[http://dx.doi.org/10.3389/fnagi.2017.00118] [PMID: 28515688]
[75]
De Felice, F.G.; Vieira, M.N.N.; Bomfim, T.R.; Decker, H.; Velasco, P.T.; Lambert, M.P.; Viola, K.L.; Zhao, W-Q.; Ferreira, S.T.; Klein, W.L. Protection of synapses against Alzheimer’s-linked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc. Natl. Acad. Sci. USA, 2009, 106(6), 1971-1976.
[http://dx.doi.org/10.1073/pnas.0809158106] [PMID: 19188609]
[76]
Yarchoan, M.; Toledo, J.B.; Lee, E.B.; Arvanitakis, Z.; Kazi, H.; Han, L-Y.; Louneva, N.; Lee, V.M-Y.; Kim, S.F.; Trojanowski, J.Q.; Arnold, S.E. Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer’s disease and tauopathies. Acta Neuropathol., 2014, 128(5), 679-689.
[http://dx.doi.org/10.1007/s00401-014-1328-5] [PMID: 25107476]
[77]
Dubey, S.K.; Lakshmi, K.K.; Krishna, K.V.; Agrawal, M.; Singhvi, G.; Saha, R.N.; Saraf, S.; Saraf, S.; Shukla, R.; Alexander, A. Insulin mediated novel therapies for the treatment of Alzheimer’s disease. Life Sci., 2020, 249, 117540.
[http://dx.doi.org/10.1016/j.lfs.2020.117540] [PMID: 32165212]
[78]
Hölscher, C. Brain insulin resistance: Role in neurodegenerative disease and potential for targeting. Expert Opin. Investig. Drugs, 2020, 29(4), 333-348.
[http://dx.doi.org/10.1080/13543784.2020.1738383] [PMID: 32175781]
[79]
Allen, S.J.; Watson, J.J.; Shoemark, D.K.; Barua, N.U.; Patel, N.K. GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacol. Ther., 2013, 138(2), 155-175.
[http://dx.doi.org/10.1016/j.pharmthera.2013.01.004] [PMID: 23348013]
[80]
Hölscher, C. Insulin, incretins and other growth factors as potential novel treatments for Alzheimer’s and Parkinson’s diseases. Biochem. Soc. Trans., 2014, 42(2), 593-599.
[http://dx.doi.org/10.1042/BST20140016] [PMID: 24646283]
[81]
Williams, B.J.; Eriksdotter-Jonhagen, M.; Granholm, A-C. Nerve growth factor in treatment and pathogenesis of Alzheimer’s disease. Prog. Neurobiol., 2006, 80(3), 114-128.
[http://dx.doi.org/10.1016/j.pneurobio.2006.09.001] [PMID: 17084014]
[82]
Counts, S.E.; Nadeem, M.; Wuu, J.; Ginsberg, S.D.; Saragovi, H.U.; Mufson, E.J. Reduction of cortical TrkA but not p75(NTR) protein in early-stage Alzheimer’s disease. Ann. Neurol., 2004, 56(4), 520-531.
[http://dx.doi.org/10.1002/ana.20233] [PMID: 15455399]
[83]
MacDonald, B.T.; He, X. Frizzled and LRP5/6 receptors for Wnt/β-catenin signaling. Cold Spring Harb. Perspect. Biol., 2012, 4(12), a007880.
[http://dx.doi.org/10.1101/cshperspect.a007880] [PMID: 23209147]
[84]
Nusse, R.; Clevers, H. Wnt/β-Catenin signaling, disease, and emerging therapeutic modalities. Cell, 2017, 169(6), 985-999.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[85]
Komiya, Y.; Habas, R. Wnt signal transduction pathways. Organogenesis, 2008, 4(2), 68-75.
[http://dx.doi.org/10.4161/org.4.2.5851] [PMID: 19279717]
[86]
Palomer, E.; Buechler, J.; Salinas, P.C. Wnt signaling deregulation in the aging and Alzheimer’s brain. Front. Cell. Neurosci., 2019, 13, 227.
[http://dx.doi.org/10.3389/fncel.2019.00227] [PMID: 31191253]
[87]
Libro, R.; Bramanti, P.; Mazzon, E. The role of the Wnt canonical signaling in neurodegenerative diseases. Life Sci., 2016, 158, 78-88.
[http://dx.doi.org/10.1016/j.lfs.2016.06.024] [PMID: 27370940]
[88]
Wan, W.; Xia, S.; Kalionis, B.; Liu, L.; Li, Y. The role of Wnt signaling in the development of Alzheimer’s disease: A potential therapeutic target? BioMed Res. Int., 2014, 2014, 301575.
[http://dx.doi.org/10.1155/2014/301575] [PMID: 24883305]
[89]
Sellers, K.J.; Elliott, C.; Jackson, J.; Ghosh, A.; Ribe, E.; Rojo, A.I.; Jarosz-Griffiths, H.H.; Watson, I.A.; Xia, W.; Semenov, M.; Morin, P.; Hooper, N.M.; Porter, R.; Preston, J.; Al-Shawi, R.; Baillie, G.; Lovestone, S.; Cuadrado, A.; Harte, M.; Simons, P.; Srivastava, D.P.; Killick, R. Amyloid β synaptotoxicity is Wnt-PCP dependent and blocked by fasudil. Alzheimers Dement., 2018, 14(3), 306-317.
[http://dx.doi.org/10.1016/j.jalz.2017.09.008] [PMID: 29055813]
[90]
Hadi, F.; Akrami, H.; Shahpasand, K.; Fattahi, M.R. Wnt signalling pathway and tau phosphorylation: A comprehensive study on known connections. Cell Biochem. Funct., 2020, 38(6), 686-694.
[http://dx.doi.org/10.1002/cbf.3530] [PMID: 32232872]
[91]
Xue, H-H.; Zhao, D-M. Regulation of mature T cell responses by the Wnt signaling pathway. Ann. N. Y. Acad. Sci., 2012, 1247, 16-33.
[http://dx.doi.org/10.1111/j.1749-6632.2011.06302.x] [PMID: 22239649]
[92]
Borrell-Pages, M.; Romero, J.C.; Crespo, J.; Juan-Babot, O.; Badimon, L. LRP5 associates with specific subsets of macrophages: Molecular and functional effects. J. Mol. Cell. Cardiol., 2016, 90, 146-156.
[http://dx.doi.org/10.1016/j.yjmcc.2015.12.002] [PMID: 26666179]
[93]
Manoharan, I.; Hong, Y.; Suryawanshi, A.; Angus-Hill, M. L.; Sun, Z.; Mellor, A. L.; Munn, D. H.; Manicassamy, S. TLR2-dependent activation of β-catenin pathway in dendritic cells induces regulatory responses and attenuates autoimmune inflammation. . Immunol. Baltim. Md 1950, 2014, 193(8), 4203-4213.
[94]
Swafford, D.; Manicassamy, S. Wnt signaling in dendritic cells: Its role in regulation of immunity and tolerance. Discov. Med., 2015, 19(105), 303-310.
[PMID: 25977193]
[95]
Caricasole, A.; Copani, A.; Caraci, F.; Aronica, E.; Rozemuller, A.J.; Caruso, A.; Storto, M.; Gaviraghi, G.; Terstappen, G.C.; Nicoletti, F. Induction of Dickkopf-1, a negative modulator of the Wnt pathway, is associated with neuronal degeneration in Alzheimer’s brain. J. Neurosci., 2004, 24(26), 6021-6027.
[http://dx.doi.org/10.1523/JNEUROSCI.1381-04.2004] [PMID: 15229249]
[96]
Blagodatski, A.; Poteryaev, D.; Katanaev, V.L. Targeting the Wnt pathways for therapies. Mol. Cell. Ther., 2014, 2, 28.
[http://dx.doi.org/10.1186/2052-8426-2-28] [PMID: 26056595]
[97]
Forlenza, O.V.; De-Paula, V.J.R.; Diniz, B.S.O. Neuroprotective effects of lithium: Implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS Chem. Neurosci., 2014, 5(6), 443-450.
[http://dx.doi.org/10.1021/cn5000309] [PMID: 24766396]
[98]
Hamano, T.; Shirafuji, N.; Makino, C.; Yen, S-H.; Kanaan, N.M.; Ueno, A.; Suzuki, J.; Ikawa, M.; Matsunaga, A.; Yamamura, O.; Kuriyama, M.; Nakamoto, Y. Pioglitazone prevents tau oligomerization. Biochem. Biophys. Res. Commun., 2016, 478(3), 1035-1042.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.016] [PMID: 27543203]
[99]
Jin, N.; Zhu, H.; Liang, X.; Huang, W.; Xie, Q.; Xiao, P.; Ni, J.; Liu, Q. Sodium selenate activated Wnt/β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer’s disease. Exp. Neurol., 2017, 297, 36-49.
[http://dx.doi.org/10.1016/j.expneurol.2017.07.006] [PMID: 28711506]
[100]
Sochocka, M.; Donskow-Łysoniewska, K.; Diniz, B.S.; Kurpas, D.; Brzozowska, E.; Leszek, J. The gut microbiome alterations and inflammation-driven pathogenesis of Alzheimer’s disease-a critical review. Mol. Neurobiol., 2019, 56(3), 1841-1851.
[http://dx.doi.org/10.1007/s12035-018-1188-4] [PMID: 29936690]
[101]
Mallick, H.; Franzosa, E.A.; Mclver, L.J.; Banerjee, S.; Sirota-Madi, A.; Kostic, A.D.; Clish, C.B.; Vlamakis, H.; Xavier, R.J.; Huttenhower, C. Predictive metabolomic profiling of microbial communities using amplicon or metagenomic sequences. Nat. Commun., 2019, 10(1), 3136.
[http://dx.doi.org/10.1038/s41467-019-10927-1] [PMID: 31316056]
[102]
Slots, J. Periodontitis: Facts, fallacies and the future. Periodontol. 2000, 2017, 75(1), 7-23.
[http://dx.doi.org/10.1111/prd.12221] [PMID: 28758294]
[103]
Tohidpour, A.; Morgun, A.V.; Boitsova, E.B.; Malinovskaya, N.A.; Martynova, G.P.; Khilazheva, E.D.; Kopylevich, N.V.; Gertsog, G.E.; Salmina, A.B. Neuroinflammation and infection: Molecular mechanisms associated with dysfunction of neurovascular unit. Front. Cell. Infect. Microbiol., 2017, 7, 276.
[http://dx.doi.org/10.3389/fcimb.2017.00276] [PMID: 28676848]
[104]
Cardoso, E.M.; Reis, C.; Manzanares-Céspedes, M.C. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad. Med., 2018, 130(1), 98-104.
[http://dx.doi.org/10.1080/00325481.2018.1396876] [PMID: 29065749]
[105]
Scannapieco, F.A.; Cantos, A. Oral inflammation and infection, and chronic medical diseases: Implications for the elderly. Periodontol. 2000, 2016, 72(1), 153-175.
[http://dx.doi.org/10.1111/prd.12129] [PMID: 27501498]
[106]
Dominy, S.S.; Lynch, C.; Ermini, F.; Benedyk, M.; Marczyk, A.; Konradi, A.; Nguyen, M.; Haditsch, U.; Raha, D.; Griffin, C.; Holsinger, L.J.; Arastu-Kapur, S.; Kaba, S.; Lee, A.; Ryder, M.I.; Potempa, B.; Mydel, P.; Hellvard, A.; Adamowicz, K.; Hasturk, H.; Walker, G.D.; Reynolds, E.C.; Faull, R.L.M.; Curtis, M.A.; Dragunow, M.; Potempa, J. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci. Adv., 2019, 5(1), eaau3333.
[http://dx.doi.org/10.1126/sciadv.aau3333] [PMID: 30746447]
[107]
Bennett, C.F. Therapeutic antisense oligonucleotides are coming of age. Annu. Rev. Med., 2019, 70, 307-321.
[http://dx.doi.org/10.1146/annurev-med-041217-010829] [PMID: 30691367]
[108]
Bishop, K.M. Progress and promise of antisense oligonucleotide therapeutics for central nervous system diseases. Neuropharmacology, 2017, 120, 56-62.
[http://dx.doi.org/10.1016/j.neuropharm.2016.12.015] [PMID: 27998711]

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