Kang Dong Min, Lukianenko Nataliia, Baik Ja-Hyun, Kim Yun Kyung, Lim Sungsu
Brain Science Institute, Korea Institute of Science and Technology (KIST), 5 Hwarang-ro 14-gil, Seongbuk-gu, Seoul, 02792, Republic of Korea.
Department of Life Sciences, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Republic of Korea.
Chembiochem. 2025 Sep 18;26(18):e202500316. doi: 10.1002/cbic.202500316. Epub 2025 Jun 27.
Amyloidogenesis is a complex process in which normally soluble proteins misfold and assemble into β-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.
淀粉样蛋白生成是一个复杂的过程，在此过程中，正常情况下可溶的蛋白质会错误折叠并组装成富含β-折叠的聚集体，即淀粉样纤维。这一病理过程与多种疾病有关，包括神经退行性疾病和全身性淀粉样变性。最近的研究表明，二硫键交联通过稳定错误折叠的中间体在促进蛋白质聚集方面起着核心作用。本综述重点介绍了导致异常二硫键形成的细胞途径，并探讨了它们对疾病进展的影响。此外，还讨论了二硫键交联的寡聚体如何抵抗降解、压倒蛋白质稳态系统并作为淀粉样纤维的前体。通过了解二硫键交联在蛋白质聚集中的作用，可以深入了解淀粉样蛋白发病机制，并确定潜在的干预治疗靶点。
