Login Register Cart 0
Generic placeholder image

Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Pathophysiology Associated with Diabetes-induced Tauopathy and Development of Alzheimer’s Disease

Author(s): Poulami Sarkar, Sarmin Banu, Sanchari Bhattacharya, Asis Bala and Debjeet Sur*

Volume 19, Issue 5, 2023

Published on: 23 August, 2022

Article ID: e130522204763 Pages: 13

DOI: 10.2174/1573399818666220513142030

Price: $65

Abstract

Alzheimer’s disease (AD) is the most common type of dementia that affects the elderly around the world. Chronic type 2 diabetes (T2DM) has been proven to be closely related to neurodegeneration, especially AD. T2DM is characterized by the cell's failure to take up insulin as well as chronic hyperglycemia. In the central nervous system, insulin plays vital regulatory roles, while in chronic hyperglycemia, it leads to the formation and accumulation of advanced glycation end products (AGEs). Inflammation plays a crucial role in development of insulin resistance in AD and T2DM. The microtubule-related protein tau is involved in the pathogenesis of several neurological diseases known as tauopathies, and is found to be abnormally hyperphosphorylated in AD and accumulated in neurons. Chronic neuroinflammation causes the breakdown of the blood-brain barrier (BBB) observed in tauopathies. The development of pro-inflammatory signaling molecules, such as cytokines, chemokines from glial cells, neurons and endothelial cells, decides the structural integrity of BBB and immune cell migration into the brain. This review highlights the use of antidiabetic compounds as promising therapeutics for AD, and also describes several new pathological molecular mechanisms associated with diabetes that increase AD pathogenesis.

Keywords: Alzheimer’s disease, type 2 diabetes mellitus, post-translational modifications, tauopathies, amyloid beta.

[1]
Diabetes. Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes (Accessed on 2021 -11 -13).
[2]
International Diabetes Federation. Diabetes is spiralling out of control. Available from: https://idf.org/ Accessed on 2021 -11 -13.
[3]
Dementia. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia (Accessed on 2021 -11 -13).
[4]
Giau VV, Bagyinszky E, Youn YC, An SSA, Kim S. APP, PSEN1, and PSEN2 mutations in Asian patients with early-onset Alzheimer disease. Int J Mol Sci 2019; 20(19): 4757.
[http://dx.doi.org/10.3390/ijms20194757] [PMID: 31557888]
[5]
Tomiyama T, Shimada H. APP Osaka mutation in familial Alzheimer’s disease-its discovery, phenotypes, and mechanism of recessive inheritance. Int J Mol Sci 2020; 21(4): E1413.
[http://dx.doi.org/10.3390/ijms21041413] [PMID: 32093100]
[6]
Morsi M, Kobeissy F, Magdeldin S, et al. A shared comparison of diabetes mellitus and neurodegenerative disorders. J Cell Biochem 2019; 120(9): 14318-25.
[http://dx.doi.org/10.1002/jcb.28094] [PMID: 30565720]
[7]
Tumminia A, Vinciguerra F, Parisi M, Frittitta L. Type 2 diabetes mellitus and Alzheimer’s disease: Role of insulin signalling and therapeutic implications. Int J Mol Sci 2018; 19(11): E3306.
[http://dx.doi.org/10.3390/ijms19113306] [PMID: 30355995]
[8]
Nguyen TT, Ta QTH, Nguyen TKO, Nguyen TTD, Giau VV. Type 3 diabetes and its role implications in Alzheimer’s disease. Int J Mol Sci 2020; 21(9): E3165.
[http://dx.doi.org/10.3390/ijms21093165] [PMID: 32365816]
[9]
Gabbouj S, Ryhänen S, Marttinen M, et al. Altered insulin signaling in Alzheimer’s disease brain - special emphasis on PI3K-Akt pathway. Front Neurosci 2019; 13: 629.
[http://dx.doi.org/10.3389/fnins.2019.00629] [PMID: 31275108]
[10]
Patel H, Dobson RJB, Newhouse SJ. A meta-analysis of Alzheimer’s disease brain transcriptomic data. J Alzheimers Dis 2019; 68(4): 1635-56.
[http://dx.doi.org/10.3233/JAD-181085] [PMID: 30909231]
[11]
Pomytkin I, Pinelis V. Brain insulin resistance: Focus on insulin receptor-mitochondria interactions. Life (Basel) 2021; 11(3): 262.
[http://dx.doi.org/10.3390/life11030262] [PMID: 33810179]
[12]
Arnold SE, Arvanitakis Z, Macauley-Rambach SL, et al. Brain insulin resistance in type 2 diabetes and Alzheimer disease: Concepts and conundrums. Nat Rev Neurol 2018; 14(3): 168-81.
[http://dx.doi.org/10.1038/nrneurol.2017.185] [PMID: 29377010]
[13]
Salas IH, De Strooper B. Diabetes and Alzheimer’s disease: A link not as simple as it seems. Neurochem Res 2019; 44(6): 1271-8.
[http://dx.doi.org/10.1007/s11064-018-2690-9] [PMID: 30523576]
[14]
Banks W A, Jaspan J B, Kastin A J, Banks W A, Jaspan J B, Kastin A J. Selective, physiological transport of insulin across the bloodbrain barrier: Novel demonstration by species-specific radioimmunoassays.
[http://dx.doi.org/10.1016/S0196-9781(97)00198-8]
[15]
Shieh JCC, Huang PT, Lin YF. Alzheimer’s disease and diabetes: Insulin signaling as the bridge linking two pathologies. Mol Neurobiol 2020; 57(4): 1966-77.
[http://dx.doi.org/10.1007/s12035-019-01858-5] [PMID: 31900863]
[16]
De Sousa RAL, Harmer AR, Freitas DA, Mendonça VA, Lacerda ACR, Leite HR. An update on potential links between type 2 diabetes mellitus and Alzheimer’s disease. Mol Biol Rep 2020; 47(8): 6347-56.
[http://dx.doi.org/10.1007/s11033-020-05693-z] [PMID: 32740795]
[17]
Gratuze M, Julien J, Petry FR, Morin F, Planel E. Insulin deprivation induces PP2A inhibition and tau hyperphosphorylation in hTau mice, a model of Alzheimer’s disease-like tau pathology. Sci Rep 2017; 7: 46359.
[http://dx.doi.org/10.1038/srep46359] [PMID: 28402338]
[18]
Craft S, Claxton A, Baker LD, et al. Effects of regular and long-acting insulin on cognition and Alzheimer’s disease biomarkers: A pilot clinical trial. J Alzheimers Dis 2017; 57(4): 1325-34.
[http://dx.doi.org/10.3233/JAD-161256] [PMID: 28372335]
[19]
Lozano L, Guevara J, Lefebvre T, et al. Effect of amyloid-Β (25-35) in hyperglycemic and hyperinsulinemic rats, effects on phosphorylation and O-GlcNAcylation of tau protein. Neuropeptides 2017; 63: 18-27.
[http://dx.doi.org/10.1016/j.npep.2017.04.001] [PMID: 28427866]
[20]
Backeström A, Papadopoulos K, Eriksson S, et al. Acute hyperglycaemia leads to altered frontal lobe brain activity and reduced working memory in type 2 diabetes. PLoS ONE 2021; 16(3 March)
[21]
Sourris KC, Watson A, Jandeleit-Dahm K. Inhibitors of advanced glycation end product (AGE) formation and accumulation. Handbook of Experimental Pharmacology. Germany: Springer Science and Business Media Deutschland GmbH 2021; 264: pp. 395-423.
[http://dx.doi.org/10.1007/164_2020_391]
[22]
Pugazhenthi S, Qin L, Reddy PH. Common neurodegenerative pathways in obesity, diabetes, and Alzheimer’s disease. Biochim Biophys Acta Mol Basis Dis 2017; 1863(5): 1037-45.
[http://dx.doi.org/10.1016/j.bbadis.2016.04.017] [PMID: 27156888]
[23]
Kirkman MS, Briscoe VJ, Clark N, et al. Diabetes in older adults. Diabetes Care 2012; 35(12): 2650-64.
[http://dx.doi.org/10.2337/dc12-1801] [PMID: 23100048]
[24]
González-Reyes RE, Aliev G, Ávila-Rodrigues M, Barreto GE. Alterations in glucose metabolism on cognition: A possible link between diabetes and dementia. JN 2016; 22(7): 812-8.
[25]
Calsolaro V, Edison P. Neuroinflammation in Alzheimer’s disease: Current evidence and future directions. Alzheimers Dement 2016; 12(6): 719-32.
[http://dx.doi.org/10.1016/j.jalz.2016.02.010] [PMID: 27179961]
[26]
Ebrahimpour S, Zakeri M, Esmaeili A. Crosstalk between obesity, diabetes, and alzheimer’s disease: Introducing quercetin as an effective triple herbal medicine. Ageing Res Rev 2020; 62: 101095.
[http://dx.doi.org/10.1016/j.arr.2020.101095] [PMID: 32535272]
[27]
Sung PS, Lin PY, Liu CH, Su HC, Tsai KJ. Neuroinflammation and neurogenesis in alzheimer’s disease and potential therapeutic approaches. Int J Mol Sci 2020; 21(3): 701.
[http://dx.doi.org/10.3390/ijms21030701] [PMID: 31973106]
[28]
Qin L, Bouchard R, Pugazhenthi S. Regulation of cyclic AMP response element-binding protein during neuroglial interactions. J Neurochem 2016; 136(5): 918-30.
[http://dx.doi.org/10.1111/jnc.13497] [PMID: 26677139]
[29]
Fang W, Bi D, Zheng R, et al. Identification and activation of TLR4-mediated signalling pathways by alginate-derived guluronate oligosaccharide in RAW264.7 macrophages. Sci Rep 2017; 7(1): 1663.
[http://dx.doi.org/10.1038/s41598-017-01868-0] [PMID: 28490734]
[30]
McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies. Neurobiol Aging 2007; 28(5): 639-47.
[http://dx.doi.org/10.1016/j.neurobiolaging.2006.03.013] [PMID: 16697488]
[31]
Choi SH, Aid S, Caracciolo L, et al. Cyclooxygenase-1 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer’s disease. J Neurochem 2013; 124(1): 59-68.
[http://dx.doi.org/10.1111/jnc.12059] [PMID: 23083210]
[32]
Finelli C. Metabolic syndrome, Alzheimer’s disease, and COVID 19: A possible correlation. Curr Alzheimer Res 2021; 18(12): 915-24.
[http://dx.doi.org/10.2174/1567205018666211209095652] [PMID: 34886772]
[33]
Naseri NN, Wang H, Guo J, Sharma M, Luo W. The complexity of tau in Alzheimer’s disease. Neurosci Lett 2019; 705: 183-94.
[http://dx.doi.org/10.1016/j.neulet.2019.04.022] [PMID: 31028844]
[34]
Silzer TK, Phillips NR. Etiology of type 2 diabetes and Alzheimer’s disease: Exploring the mitochondria. Mitochondrion 2018; 43: 16-24.
[http://dx.doi.org/10.1016/j.mito.2018.04.004] [PMID: 29678670]
[35]
Ahmad W, Ijaz B, Shabbiri K, Ahmed F, Rehman S. Oxidative toxicity in diabetes and Alzheimer’s disease: Mechanisms behind ROS/RNS generation. J Biomed Sci 2017; 24(1): 76.
[http://dx.doi.org/10.1186/s12929-017-0379-z] [PMID: 28927401]
[36]
Bhatti JS, Tamarai K, Kandimalla R, et al. Protective effects of a mitochondria-targeted small peptide SS31 against hyperglycemia-induced mitochondrial abnormalities in the liver tissues of diabetic mice, Tallyho/JngJ mice. Mitochondrion 2021; 58: 49-58.
[http://dx.doi.org/10.1016/j.mito.2021.02.007] [PMID: 33639273]
[37]
Hanyu H, Takenoshita N, Fukasawa R, et al. Diabetes-related dementia is associated with tau pathology rather than amyloid pathology. J Neurol Sci 2017; 381: 328.
[http://dx.doi.org/10.1016/j.jns.2017.08.932]
[38]
Tai J, Liu W, Li Y, Li L, Hölscher C. Neuroprotective effects of a triple GLP-1/GIP/glucagon receptor agonist in the APP/PS1 transgenic mouse model of Alzheimer’s disease. Brain Res 2018; 1678: 64-74.
[http://dx.doi.org/10.1016/j.brainres.2017.10.012] [PMID: 29050859]
[39]
Shoshan-Barmatz V, Nahon-Crystal E, Shteinfer-Kuzmine A, Gupta R. VDAC1, mitochondrial dysfunction, and Alzheimer’s disease. Pharmacol Res 2018; 131: 87-101.
[http://dx.doi.org/10.1016/j.phrs.2018.03.010] [PMID: 29551631]
[40]
Dixit S, Fessel JP, Harrison FE. Mitochondrial dysfunction in the APP/PSEN1 mouse model of Alzheimer’s disease and a novel protective role for ascorbate. Free Radic Biol Med 2017; 112: 515-23.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.08.021] [PMID: 28863942]
[41]
Garabadu D, Verma J. Exendin-4 attenuates brain mitochondrial toxicity through PI3K/Akt-dependent pathway in amyloid beta (1-42)-induced cognitive deficit rats. Neurochem Int 2019; 128: 39-49.
[http://dx.doi.org/10.1016/j.neuint.2019.04.006] [PMID: 31004737]
[42]
Johnson GVW, Stoothoff WH. Tau phosphorylation in neuronal cell function and dysfunction. J Cell Sci 2004; 117(Pt 24): 5721-9.
[http://dx.doi.org/10.1242/jcs.01558] [PMID: 15537830]
[43]
Gong CX, Liu F, Grundke-Iqbal I, Iqbal K. Post-translational modifications of tau protein in Alzheimer’s disease. J Neural Transm (Vienna) 2005; 112(6): 813-38.
[http://dx.doi.org/10.1007/s00702-004-0221-0] [PMID: 15517432]
[44]
Michalicova A, Majerova P, Kovac A. Tau protein and its role in blood-brain barrier dysfunction. Front Mol Neurosci 2020; 13: 570045.
[http://dx.doi.org/10.3389/fnmol.2020.570045] [PMID: 33100967]
[45]
Park S, Lee JH, Jeon JH, Lee MJ. Degradation or aggregation: The ramifications of post-translational modifications on tau. BMB Reports. The Biochemical Society of the Republic of Korea 2018; 51(6): 265-73.
[http://dx.doi.org/10.5483/BMBRep.2018.51.6.077]
[46]
Almansoub HAMM, Tang H, Wu Y, et al. Tau abnormalities and the potential therapy in Alzheimer’s disease. J Alzheimers Dis 2019; 67(1): 13-33.
[http://dx.doi.org/10.3233/JAD-180868] [PMID: 30507581]
[47]
Abbondante S, Baglietto-Vargas D, Rodriguez-Ortiz CJ, Estrada-Hernandez T, Medeiros R, Laferla FM. Genetic ablation of tau mitigates cognitive impairment induced by type 1 diabetes. Am J Pathol 2014; 184(3): 819-26.
[http://dx.doi.org/10.1016/j.ajpath.2013.11.021] [PMID: 24412516]
[48]
El Khoury NB, Gratuze M, Papon MA, Bretteville A, Planel E. Insulin dysfunction and tau pathology. Front Cell Neurosci 2014; 8: 22.
[http://dx.doi.org/10.3389/fncel.2014.00022] [PMID: 24574966]
[49]
Kimura N. Diabetes mellitus induces Alzheimer’s disease pathology: Histopathological evidence from animal models. Int J Mol Sci 2016; 17(4): 503.
[http://dx.doi.org/10.3390/ijms17040503] [PMID: 27058526]
[50]
Martin L, Latypova X, Terro F. Post-translational modifications of tau protein: Implications for Alzheimer’s disease. Neurochem Int 2011; 58(4): 458-71.
[http://dx.doi.org/10.1016/j.neuint.2010.12.023]
[51]
Chong FP, Ng KY, Koh RY, Chye SM. Tau proteins and tauopathies in Alzheimer’s disease. Cell Mol Neurobiol 2018; 38(5): 965-80.
[http://dx.doi.org/10.1007/s10571-017-0574-1] [PMID: 29299792]
[52]
Baglietto-Vargas D, Shi J, Yaeger DM, Ager R, LaFerla FM. Diabetes and Alzheimer’s disease crosstalk. Neurosci Biobehav Rev 2016; 64: 272-87.
[http://dx.doi.org/10.1016/j.neubiorev.2016.03.005] [PMID: 26969101]
[53]
Jesu´ J, Avila J, Lucas J J. Role of tau protein in both physiological and pathological conditions. JN 2004; 84(2): 361-84.
[54]
García-Sierra F, Mondragón-Rodríguez S, Basurto-Islas G. Truncation of tau protein and its pathological significance in Alzheimer’s disease. J Alzheimers Dis 2008; 14(4): 401-9.
[http://dx.doi.org/10.3233/JAD-2008-14407] [PMID: 18688090]
[55]
Gu J, Xu W, Jin N, et al. Truncation of tau selectively facilitates its pathological activities. J Biol Chem 2020; 295(40): 13812-28.
[http://dx.doi.org/10.1074/jbc.RA120.012587] [PMID: 32737201]
[56]
Kovac A, Zilkova M, Deli MA, Zilka N, Novak M. Human truncated tau is using a different mechanism from amyloid-β to damage the blood-brain barrier. J Alzheimers Dis 2009; 18(4): 897-906.
[http://dx.doi.org/10.3233/JAD-2009-1197] [PMID: 19749439]
[57]
Yamazaki Y, Kanekiyo T. Blood-brain barrier dysfunction and the pathogenesis of Alzheimer’s disease. Int J Mol Sci 2017; 18(9): E1965.
[http://dx.doi.org/10.3390/ijms18091965] [PMID: 28902142]
[58]
Cao Y, Hölscher C, Hu MM, et al. DA5-CH, a novel GLP-1/GIP dual agonist, effectively ameliorates the cognitive impairments and pathology in the APP/PS1 mouse model of Alzheimer’s disease. Eur J Pharmacol 2018; 827: 215-26.
[http://dx.doi.org/10.1016/j.ejphar.2018.03.024] [PMID: 29551659]
[59]
Li C, Liu W, Li X, et al. The novel GLP-1/GIP analogue DA5-CH reduces tau phosphorylation and normalizes theta rhythm in the icv. STZ rat model of AD. Brain Behav 2020; 10(3): e01505.
[http://dx.doi.org/10.1002/brb3.1505] [PMID: 31960630]
[60]
Salles GN, Calió ML, Hölscher C, Pacheco-Soares C, Porcionatto M, Lobo AO. Neuroprotective and restorative properties of the GLP-1/GIP dual agonist DA-JC1 compared with a GLP-1 single agonist in Alzheimer’s disease. Neuropharmacology 2020; 162: 107813.
[http://dx.doi.org/10.1016/j.neuropharm.2019.107813] [PMID: 31628935]
[61]
Jantrapirom S, Nimlamool W, Chattipakorn N, et al. Liraglutide suppresses tau hyperphosphorylation, amyloid beta accumulation through regulating neuronal insulin signaling and BACE-1 Activity. Int J Mol Sci 2020; 21(5): E1725.
[http://dx.doi.org/10.3390/ijms21051725] [PMID: 32138327]
[62]
Batista AF, Forny-Germano L, Clarke JR, et al. The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer’s disease. J Pathol 2018; 245(1): 85-100.
[http://dx.doi.org/10.1002/path.5056] [PMID: 29435980]
[63]
Femminella GD, Frangou E, Love SB, et al. Evaluating the effects of the novel GLP-1 analogue liraglutide in Alzheimer’s disease: Study protocol for a randomised controlled trial (ELAD study). Trials 2019; 20(1): 191.
[http://dx.doi.org/10.1186/s13063-019-3259-x] [PMID: 30944040]
[64]
K C S , Kakoty V, Marathe S, Chitkara D, Taliyan R. Exploring the neuroprotective potential of rosiglitazone embedded nanocarrier system on streptozotocin induced mice model of Alzheimer’s disease. Neurotox Res 2021; 39(2): 240-55.
[http://dx.doi.org/10.1007/s12640-020-00258-1] [PMID: 32683650]
[65]
Cortez I, Hernandez CM, Dineley KT. Enhancement of select cognitive domains with rosiglitazone implicates dorsal hippocampus circuitry sensitive to PPARγ agonism in an Alzheimer’s mouse model. Brain Behav 2021; 11(2): e01973.
[http://dx.doi.org/10.1002/brb3.1973] [PMID: 33382528]
[66]
Kenawy S, Hegazy R, Hassan A, et al. Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin. PLoS One 2017; 12(8): e0183565.
[http://dx.doi.org/10.1371/journal.pone.0183565] [PMID: 28832656]
[67]
Chen S, Zhou M, Sun J, et al. DPP-4 inhibitor improves learning and memory deficits and AD-like neurodegeneration by modulating the GLP-1 signaling. Neuropharmacology 2019; 157: 107668.
[http://dx.doi.org/10.1016/j.neuropharm.2019.107668] [PMID: 31199957]
[68]
Dong Q, Teng SW, Wang Y, et al. Sitagliptin protects the cognition function of the Alzheimer’s disease mice through activating glucagon-like peptide-1 and BDNF-TrkB signalings. Neurosci Lett 2019; 696: 184-90.
[http://dx.doi.org/10.1016/j.neulet.2018.12.041] [PMID: 30597232]
[69]
Isik AT, Soysal P, Yay A, Usarel C. The effects of sitagliptin, a DPP-4 inhibitor, on cognitive functions in elderly diabetic patients with or without Alzheimer’s disease. Diabetes Res Clin Pract 2017; 123: 192-8.
[http://dx.doi.org/10.1016/j.diabres.2016.12.010] [PMID: 28056430]
[70]
Cai HY, Yang JT, Wang ZJ, et al. Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer’s disease. Biochem Biophys Res Commun 2018; 495(1): 1034-40.
[http://dx.doi.org/10.1016/j.bbrc.2017.11.114] [PMID: 29175324]
[71]
Ma QH, Jiang LF, Mao JL, Xu WX, Huang M. Vildagliptin prevents cognitive deficits and neuronal apoptosis in a rat model of Alzheimer’s disease. Mol Med Rep 2018; 17(3): 4113-9.
[http://dx.doi.org/10.3892/mmr.2017.8289] [PMID: 29257340]
[72]
Dokumacı AH, Yerer Aycan MB. Vildagliptine protects SH-SY5Y human neuron-like cells from Aβ 1-42 induced toxicity, in vitro. Cytotechnology 2019; 71(2): 635-46.
[http://dx.doi.org/10.1007/s10616-019-00312-7] [PMID: 30968232]
[73]
Zhou M, Chen S, Peng P, et al. Dulaglutide ameliorates STZ induced AD-like impairment of learning and memory ability by modulating hyperphosphorylation of tau and NFs through GSK3β. Biochem Biophys Res Commun 2019; 511(1): 154-60.
[http://dx.doi.org/10.1016/j.bbrc.2019.01.103] [PMID: 30773255]
[74]
Farr SA, Roesler E, Niehoff ML, Roby DA, McKee A, Morley JE. Metformin improves learning and memory in the SAMP8 mouse model of Alzheimer’s disease. J Alzheimers Dis 2019; 68(4): 1699-710.
[http://dx.doi.org/10.3233/JAD-181240] [PMID: 30958364]
[75]
Kickstein E, Krauss S, Thornhill P, et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci USA 2010; 107(50): 21830-5.
[http://dx.doi.org/10.1073/pnas.0912793107] [PMID: 21098287]
[76]
Aksoz E, Gocmez SS, Sahin TD, Aksit D, Aksit H, Utkan T. The protective effect of metformin in scopolamine-induced learning and memory impairment in rats. Pharmacol Rep 2019; 71(5): 818-25.
[http://dx.doi.org/10.1016/j.pharep.2019.04.015] [PMID: 31382167]
[77]
Syal C, Kosaraju J, Hamilton L, et al. Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer’s disease. Theranostics 2020; 10(14): 6337-60.
[http://dx.doi.org/10.7150/thno.44962] [PMID: 32483456]
[78]
Mostafa DK, Ismail CA, Ghareeb DA. Differential metformin dose-dependent effects on cognition in rats: Role of Akt. Psychopharmacology (Berl) 2016; 233(13): 2513-24.
[http://dx.doi.org/10.1007/s00213-016-4301-2] [PMID: 27113224]
[79]
Swaraz AM, Sultana F, Bari MW, et al. Phytochemical profiling of Blumea laciniata (Roxb.) DC. and its phytopharmaceutical potential against diabetic, obesity, and Alzheimer’s. Biomed Pharmacother 2021; 141: 111859.
[http://dx.doi.org/10.1016/j.biopha.2021.111859]
[80]
Poorgholam P, Yaghmaei P, Noureddini M, Hajebrahimi Z. Effects of artemisinin and TSP 1 human endometrial derived stem cells on a streptozocin induced model of Alzheimer’s disease and diabetes in Wistar rats. Acta Neurobiol Exp (Wars) 2021; 81(2): 141-51.

Rights & Permissions Print Cite
Article Metrics
7
© 2024 Bentham Science Publishers | Privacy Policy