Amyloid assembly and disassembly

作者：Chuang Edward; Hori Acacia M; Hesketh Christina D; Shorter James^*

来源：Journal of Cell Science, 2018, 131(8): UNSP jcs189928.

DOI：10.1242/jcs.189928

• Amyloid
• Autophagy
• Disaggregase
• Prion
• Neurodegeneration

Amyloid fibrils are protein homopolymers that adopt diverse cross-beta conformations. Some amyloid fibrils are associated with the pathogenesis of devastating neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. Conversely, functional amyloids play beneficial roles in melanosome biogenesis, long-term memory formation and release of peptide hormones. Here, we showcase advances in our understanding of amyloid assembly and structure, and how distinct amyloid strains formed by the same protein can cause distinct neurodegenerative diseases. We discuss how mutant steric zippers promote deleterious amyloidogenesis and aberrant liquid-to-gel phase transitions. We also highlight effective strategies to combat amyloidogenesis and related toxicity, including: (1) small-molecule drugs (e.g. tafamidis) to inhibit amyloid formation or (2) stimulate amyloid degradation by the proteasome and autophagy, and (3) protein disaggregases that disassemble toxic amyloid and soluble oligomers. We anticipate that these advances will inspire therapeutics for several fatal neurodegenerative diseases.

• 出版日期2018-4-15