Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8837954 | Behavioural Brain Research | 2018 | 27 Pages |
Abstract
It is well known that Alzheimer's disease (AD) is closely related to diabetes mellitus (DM), and AD is also regarded as Type 3 diabetes (T3D). However, the exact link between AD and DM is still unclear. Recently, more and more evidence has shown that glycogen synthase kinase-3β (GSK-3β) may be the potential link between DM and AD. In DM, GSK-3β is the crucial enzyme of glycogen synthesis, which plays a key role in regulating blood glucose. More importantly, GSK-3β is one of the key factors leading to insulin deficiency and insulin resistance, and insulin resistance is an important hallmark of the occurrence and development of DM. In AD, GSK-3β plays an important role in hyperphosphorylation of microtubule-associated protein tau (tau), which is one of the pathological features in AD. GSK-3β is one of the important kinases of tau phosphorylation and is involved in the insulin/phosphoinositide 3-kinase/protein kinase B (insulin/PI3K/Akt) signaling pathway. Dysfunction of the insulin/PI3K/Akt signaling pathway, which regulates glucose metabolism in the brain, can lead to tau hyperphosphorylation in the brain of AD patents. Additionally, insulin resistance in DM may cause β-amyloid (Aβ) deposition, which will be cleared by tau, but excessive phosphorylation of tau will further aggravate the neurotoxicity; then damage the brain and affect the cognitive function. GSK-3β is considered as a common kinase in insulin signaling transduction and tau protein phosphorylation, so we have reasons to believe that GSK-3β is a potential link between DM and AD.
Keywords
phosphoinositide-dependent protein kinase 1PS1GDSPP-1NFTsMMSEGPCRsIRS-1GSK-3βIGF-1FFAsAPPGCAPDX-1iNOSAβSPSJnkPDK1NODPI3KADAS-CogSTAT3CREBG protein-coupled receptorspresenilin 1β-AmyloidAktFree fatty acidsinsulin-like growth factor-1insulin receptor substrate-1Mini-Mental Status ExaminationAlzheimer’s diseaseDiabetes mellitusNon-obese diabeticinducible nitric oxide synthasesenile plaquesphosphoinositide 3-kinaseGeriatric Depression Scaleneurofibrillary tanglescAMP-response element binding proteinprotein phosphatase 1amyloid precursor proteinprotein kinase BGlycogen synthase kinase-3βglycogen synthase
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Authors
Ying Zhang, Nan-qu Huang, Fei Yan, Hai Jin, Shao-yu Zhou, Jing-shan Shi, Feng Jin,