Issue 46, 2019

Fundamentals of cross-seeding of amyloid proteins: an introduction

Abstract

Misfolded protein aggregates formed by the same (homologous) or different (heterologous/cross) sequences are the pathological hallmarks of many protein misfolding diseases (PMDs) including Alzheimer's disease (AD) and type 2 diabetes (T2D). Different from homologous-amyloid aggregation that is solely associated with a specific PMD, cross-amyloid aggregation (i.e. cross-seeding) of different amyloid proteins is more fundamentally and biologically important for understanding and untangling not only the pathological process of each PMD, but also a potential molecular cross-talk between different PMDs. However, the cross-amyloid aggregation is still a subject poorly explored and little is known about its sequence/structure-dependent aggregation mechanisms, as compared to the widely studied homo-amyloid aggregation. Here, we review the most recent and important findings of amyloid cross-seeding behaviors from in vitro, in vivo, and in silico studies. Some typical cross-seeding phenomena between Aβ/hIAPP, Aβ/tau, Aβ/α-synuclein, and tau/α-synuclein are selected and presented, and the underlying specific or general cross-seeding mechanisms are also discussed to better reveal their sequence–structure–property relationships. The potential use of the cross-seeding concept to design amyloid inhibitors is also proposed. Finally, we offer some personal perspectives on current major challenges and future research directions in this less-studied yet important field, and hopefully this work will stimulate more research to explore all possible fundamental and practical aspects of amyloid cross-seeding.

Graphical abstract: Fundamentals of cross-seeding of amyloid proteins: an introduction

Article information

Article type
Review Article
Submitted
30 ago 2019
Accepted
03 out 2019
First published
07 out 2019

J. Mater. Chem. B, 2019,7, 7267-7282

Author version available

Fundamentals of cross-seeding of amyloid proteins: an introduction

B. Ren, Y. Zhang, M. Zhang, Y. Liu, D. Zhang, X. Gong, Z. Feng, J. Tang, Y. Chang and J. Zheng, J. Mater. Chem. B, 2019, 7, 7267 DOI: 10.1039/C9TB01871A

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements