Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong 793022, India.
Department of Biotechnology, National Institute of Technology Warangal, Warangal 506004, India.
Molecules. 2022 Mar 8;27(6):1776. doi: 10.3390/molecules27061776.
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.
大多数神经退行性疾病，如阿尔茨海默病、2 型糖尿病、帕金森病等，都是由包含错误折叠蛋白聚集物的包涵体和斑块引起的。这些蛋白聚集物本质上是由相同（同源）或不同（异源）序列的相互作用形成的。一些实验证据表明淀粉样蛋白中存在交叉引发现象，导致多组分组装；然而，分子和结构细节仍未得到充分探索。在这里，我们详细讨论了淀粉样蛋白和交叉引发现象。有数据表明，针对相互作用的淀粉样蛋白的共同表位可能是比仅针对一种物质更好的治疗选择。我们还研究了针对参与交叉引发事件的淀粉样蛋白的双抑制剂。还考虑了理解机制和开发治疗方法的未来范围和主要挑战。对淀粉样蛋白交叉引发的详细了解将刺激实际方面的进一步研究，并更好地设计抗淀粉样蛋白治疗方法。
