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

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.

• Authors: Ying Zhang, Nan-Qu Huang, Fei Yan, Hai Jin, Shao-Yu Zhou, Jing-Shan Shi, Feng Jin
• Journal: Behavioural brain research (Behav Brain Res) Vol. 339 Pg. 57-65 (Feb 26 2018) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 29158110 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Insulin
• tau Proteins
• Glycogen Synthase Kinase 3 beta

Topics

• Alzheimer Disease (metabolism, pathology)
• Amyloid beta-Peptides (metabolism)
• Animals
• Diabetes Mellitus (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• Insulin (metabolism)
• tau Proteins (metabolism)