Reciprocal Molecular Interactions between the Aβ Peptide Linked to Alzheimer's Disease and Insulin Linked to Diabetes Mellitus Type II

ACS Chemical Neuroscience
Jinghui LuoJan Pieter Abrahams

Abstract

Clinical studies indicate diabetes mellitus type II (DM) doubles the risk that a patient will also develop Alzheimer's disease (AD). DM is caused by insulin resistance and a relative lack of active insulin. AD is characterized by the deposition of amyloid β (Aβ) peptide fibrils. Prior to fibrillating, Aβ forms intermediate, prefibrillar oligomers, which are more cytotoxic than the mature Aβ fibrils. Insulin can also form amyloid fibrils. In vivo studies have revealed that insulin promotes the production of Aβ, and that soluble Aβ competes with insulin for the insulin receptor. Here, we report that monomeric insulin interacted with soluble Aβ and that both molecules reciprocally slowed down the aggregation kinetics of the other. Prefibrillar oligomers of Aβ that eventually formed in the presence of insulin were less cytotoxic than Aβ oligomers formed in the absence of insulin. Mature Aβ fibrils induced fibrillation of soluble insulin, but insulin aggregates did not promote Aβ fibrillation. Our study indicates that direct molecular interactions between insulin and Aβ may contribute to the strong link between DM and AD.

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Citations

Sep 7, 2018·Frontiers in Pharmacology·Aminu Mohammed, Md Shahidul Islam
Jul 1, 2020·International Journal of Molecular Sciences·Ya-Ru Huang, Rui-Tian Liu
Feb 13, 2021·The Journal of Physical Chemistry Letters·Kailash P PrajapatiKarunakar Kar
Jun 12, 2017·ACS Biomaterials Science & Engineering·Bibin G AnandKarunakar Kar

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