Amyloid cross-seeding between Aβ and hIAPP in relation to the pathogenesis of Alzheimer and type 2 diabetes

Amyloid cross-seeding of different amyloid proteins is considered as a highly possible mechanism for exacerbating the transmissible pathogenesis of protein misfolding disease (PMDs) and for explaining a molecular link between different PMDs, including Alzheimer disease (AD) and type 2 diabetes (T2D), AD and Parkinson disease (PD), and AD and prion disease. Among them, AD and T2D are the most prevalent PMDs, affecting millions of people globally, while A beta and hIAPP are the causative peptides responsible for AD and T2D, respectively. Increasing clinical and epidemiological evidences lead to a hypothesis that the cross-seeding of A beta and hIAPP is more biologically responsible for a pathological link between AD and T2D. In this review, we particularly focus on (i) the most recent and important findings of amyloid cross-seeding between A beta and hIAPP from in vitro, in vivo, and in silico studies, (ii) a mechanistic role of structural compatibility and sequence similarity of amyloid proteins (beyond A beta and hIAPP) in amyloid cross-seeding, and (iii) several current challenges and future research directions in this lessstudied field. Review of amyloid cross-seeding hopefully provides some mechanistic understanding of amyloidogenesis and inspires more efforts for the better design of next-generation drugs/strategies to treat different PMDs simultaneously. (C) 2020 The Chemical Industry and Engineering Society of China, and Chemical Industry Press Co., Ltd. All rights reserved.

Automated summary

The research focuses on the mechanism of amyloid cross-seeding between Aβ and hIAPP and its connection between AD and T2D, explores the role of structural compatibility and sequence similarity of amyloid proteins in cross-seeding, and proposes current challenges and future research directions in this less-studied field.