2015
DOI: 10.1111/jnc.13248
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Early intervention with glucagon‐like peptide 1 analog liraglutide prevents tau hyperphosphorylation in diabetic db/db mice

Abstract: Increasing evidence has shown that type 2 diabetes (T2D) is a risk factor for Alzheimer's disease. Neurofibrillary tangles, which consist of hyperphosphorylated tau and misfolded microtubules, is one of the neuropathological hallmarks of Alzheimer's disease. Db/db mice, a rodent model of T2D, also exhibited age-dependent tau hyperphosphorylation. Glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, has been found to have neuroprotective effects. The aim of this study was to explore the potenti… Show more

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Cited by 54 publications
(34 citation statements)
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“…In view of the fact that increased levels of phosphorylated IRS-1 has been identified as the primary cause of neuronal insulin resistance in AD, (and have also been implicated in PD) exenatide and liraglutide have also demonstrated the ability to reduce levels of IRS-1 pS616 and IRS-1 pS36 in the APP/PS1 model of AD and diabetic mice. This has been shown to not only lead to facilitation of insulin signalling, but the restoration of normal tissue responses to insulin (Bomfim et al, 2012;Long-Smith et al, 2013;Ma et al, 2015), resulting in improvements in AD pathology and functional improvements in cognition. These beneficial effects on neuronal insulin resistance and restoration of insulin signalling essentially restores and increases the basal activation of the AKT pathway, activating signalling cascades that ultimately promote cellular survival.…”
Section: Glucagon-like Peptide-1(glp-1) Analogsmentioning
confidence: 99%
“…In view of the fact that increased levels of phosphorylated IRS-1 has been identified as the primary cause of neuronal insulin resistance in AD, (and have also been implicated in PD) exenatide and liraglutide have also demonstrated the ability to reduce levels of IRS-1 pS616 and IRS-1 pS36 in the APP/PS1 model of AD and diabetic mice. This has been shown to not only lead to facilitation of insulin signalling, but the restoration of normal tissue responses to insulin (Bomfim et al, 2012;Long-Smith et al, 2013;Ma et al, 2015), resulting in improvements in AD pathology and functional improvements in cognition. These beneficial effects on neuronal insulin resistance and restoration of insulin signalling essentially restores and increases the basal activation of the AKT pathway, activating signalling cascades that ultimately promote cellular survival.…”
Section: Glucagon-like Peptide-1(glp-1) Analogsmentioning
confidence: 99%
“…Liraglutide, a glucagon-like peptide 1 (GLP-1) analog that stimulates insulin secretion, prevents aberrant tau phosphorylation in a mouse model of type II diabetes [55] and significantly reduces aberrantly phosphorylated tau and improves motor function in a mouse model of tauopathy (hTauP301L) [56]. Similarly, linagliptin has also recently been reported to reduce aberrant tau phosphorylation and improve cognition in 3xTg-AD mice [57].…”
Section: Stimulators Of Pathogenic Tau Formationmentioning
confidence: 99%
“…The mechanistic link between AD and diabetes is still unknown and recent literature suggesting inflammatory response, IR insulin growth factor (IGF) signaling, ApoEε4 allele on synaptic plasticity, acetylcholine esterase activity and vascular dysregulation of brain capillaries would play crucial role in forming pathophysiologic changes relating diabetes to dementia, including white matter disease, breakdown of the blood brain barrier, inflammation, and others [4958]. Type 3 diabetes also effects glycogen synthase kinase 3β (GSK3β) signaling on Tau phosphorylation, and thus effect on mitochondria in terms to decrease or loss of ATP production [5154] (Figure 2). …”
Section: Type 3 Diabetesmentioning
confidence: 99%