Zhang Chunlan, Huang Xufei, Li Jian
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Blood Rev. 2017 Jul;31(4):261-270. doi: 10.1016/j.blre.2017.03.002. Epub 2017 Mar 8.
Amyloid light-chain (AL) amyloidosis is a plasma-cell dyscrasia, as well as the most common type of systematic amyloidosis. Pathogenic plasma cells that have distinct cytogenetic and molecular properties secrete an excess amount of amyloidogenic light chains. Assisted by post-translational modifications, matrix components, and other environmental factors, these light chains undergo a conformational change that triggers the formation of amyloid fibrils that overrides the extracellular protein quality control system. Moreover, the amyloidogenic light-chain itself is cytotoxic. As a consequence, organ dysfunction is caused by both organ architecture disruption and the direct cytotoxic effect of amyloidogenic light chains. Here, we reviewed the molecular mechanisms underlying this sequence of events that ultimately leads to AL amyloidosis and also discuss current in vitro and in vivo models, as well as relevant novel therapeutic approaches.
淀粉样轻链（AL）淀粉样变性是一种浆细胞发育异常，也是最常见的系统性淀粉样变性类型。具有独特细胞遗传学和分子特性的致病性浆细胞分泌过量的淀粉样生成轻链。在翻译后修饰、基质成分和其他环境因素的辅助下，这些轻链发生构象变化，触发淀粉样纤维的形成，从而超越细胞外蛋白质质量控制系统。此外，淀粉样生成轻链本身具有细胞毒性。因此，器官功能障碍是由器官结构破坏和淀粉样生成轻链的直接细胞毒性作用共同引起的。在这里，我们回顾了最终导致AL淀粉样变性这一系列事件的分子机制，并讨论了当前的体外和体内模型以及相关的新型治疗方法。
