Amyloid Cross-Seeding: Mechanism, Implication, and Inhibition

Molecules

Prakash Saudagar¹  Santanu Sasidharan¹  Timir Tripathi²  Sushma Subedi²  Niharika Nag² 

[1] Department of Biotechnology, National Institute of Technology Warangal, Warangal 506004, India;Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India;

关键词: amyloid proteins;    aggregation;    cross-seeding;    protein misfolding diseases;    dual inhibition;    fibrillation;   

DOI  :  10.3390/molecules27061776

来源: DOAJ

【 摘 要 】

Most neurodegenerative diseases such as Alzheimer’s disease, type 2 diabetes, Parkinson’s disease, etc. are caused by inclusions and plaques containing misfolded protein aggregates. These protein aggregates are essentially formed by the interactions of either the same (homologous) or different (heterologous) sequences. Several experimental pieces of evidence have revealed the presence of cross-seeding in amyloid proteins, which results in a multicomponent assembly; however, the molecular and structural details remain less explored. Here, we discuss the amyloid proteins and the cross-seeding phenomena in detail. Data suggest that targeting the common epitope of the interacting amyloid proteins may be a better therapeutic option than targeting only one species. We also examine the dual inhibitors that target the amyloid proteins participating in the cross-seeding events. The future scopes and major challenges in understanding the mechanism and developing therapeutics are also considered. Detailed knowledge of the amyloid cross-seeding will stimulate further research in the practical aspects and better designing anti-amyloid therapeutics.

【 授权许可】

Unknown