期刊
CHINESE JOURNAL OF CHEMICAL ENGINEERING
卷 30, 期 -, 页码 225-235出版社
CHEMICAL INDUSTRY PRESS CO LTD
DOI: 10.1016/j.cjche.2020.09.033
关键词
Amyloid peptide; Amyloid aggregation; Amyloid cross-seeding; Amyloid-beta; hIAPP; Protein misfolding
资金
- NSF [CBET-1510099, DMR-1806138, CMMI-1825122]
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.
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.
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