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Fundamentals and Introductory of Cross-seeding of Amyloid Proteins


Misfolded protein aggregates formed by the same (homologous) or different sequences (heterologous/cross) sequences are the pathological hallmarks of many protein misfolding diseases (PMDs) including Alzheimer 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 are 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 presented, and the underlying specific or general cross-seeding mechanisms are also discussed to better reveal their sequence-structure-property relationship. The potential use of 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 will stimulate more research to explore all possible fundamental and practical aspects of amyloid cross-seeding.

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Publication details

The article was received on 30 Aug 2019, accepted on 03 Oct 2019 and first published on 07 Oct 2019

Article type: Review Article
DOI: 10.1039/C9TB01871A
J. Mater. Chem. B, 2019, Accepted Manuscript

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    Fundamentals and Introductory of Cross-seeding of Amyloid Proteins

    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, Accepted Manuscript , DOI: 10.1039/C9TB01871A

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