Pathological Disulfide Bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression

초록

Amyloidogenesis is a complex process in which normally soluble proteins misfold and assemble into beta-sheet-rich aggregates known as amyloid fibrils. This pathological process is implicated in a broad range of diseases, including neurodegenerative disorders and systemic amyloidosis. Recent studies indicate that disulfide-crosslinking plays a central role in promoting protein aggregation by stabilizing misfolded intermediates. This review highlights the cellular pathways leading to abnormal disulfide bond formation and examines their impact on disease progression. Additionally, a discussion is made on how disulfide-crosslinked oligomeric species resist degradation, overwhelm proteostasis systems, and serve as precursors for amyloid fibrils. By understanding the role of disulfide crosslinks in protein aggregation, insights into amyloid pathogenesis are gained and potential therapeutic targets for intervention are identified.

키워드