Cited by 301Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchAldose Reductase and Taurine

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Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link

Zhang, Ying, Huang, Nan-qu, Yan, Fei, Jin, Hai, Zhou, Shao-yu, Shi, Jing-shan, Jin, Feng·2018·Behavioural Brain Research

DOI 10.1016/j.bbr.2017.11.015

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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.

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Authors: Zhang, Y., Huang, N.-Q., Yan, F., Jin, H., Zhou, S.-Y., Shi, J.-S., & Jin, F.
Affiliations: Zunyi Medical University (CN)
Corresponding author: Jin, Hai
Jin, Feng
ORCID: Zhang, Ying
Yan, Fei
Jin, Hai
Jin, Feng
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2018-02
Volume: 339
Pages: 57-65
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2017.11.015
OpenAlex: W2770586248
Cited by: 301
References: 130
Citations by year: 2026: 28 · 2025: 38 · 2024: 45 · 2023: 48 · 2022: 42 · 2021: 38 · 2020: 37 · 2019: 14 · 2018: 10
FWCI: 2.05
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Natural Science Foundation of China (81660599, 81360311, 81460548)
Postgraduate Education Foundation of Guizhou Province (KYJJ2017008)
Zunyi Medical University Funds (2013F-686, F-738)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
Keywords: diabetes mellitus, Alzheimer's disease, glycogen synthase kinase-3β, type 3 diabetes, insulin resistance, tau hyperphosphorylation, amyloid-beta deposition, glycogen synthesis, neurotoxicity
MeSH terms: Glycogen Synthase Kinase 3 beta, Alzheimer Disease, Animals, Diabetes Mellitus, Humans, Insulin, Amyloid beta-Peptides, tau Proteins

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Diabetes mellitus and Alzheimer's disease: GSK-3β as a potential link

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