Light chain amyloidosis: Where are the light chains from and how they play their pathogenic role?

被引:20
|
作者
Zhang, Chunlan
Huang, Xufei
Li, Jian [1 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Hematol, Beijing 100730, Peoples R China
基金
中国国家自然科学基金;
关键词
Light-chain amyloidosis; Pathogenesis; Molecular mechanism; Fibrillogenesis; Cytotoxicity; STEM-CELL TRANSPLANTATION; PRIMARY SYSTEMIC AMYLOIDOSIS; BETA-PEPTIDE DEPOSITION; AL PRIMARY AMYLOIDOSIS; HUMAN MESANGIAL CELLS; BENCE-JONES PROTEINS; HIGH-DOSE MELPHALAN; P-COMPONENT; CARDIAC INVOLVEMENT; ALZHEIMERS-DISEASE;
D O I
10.1016/j.blre.2017.03.002
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2017 Elsevier Ltd. All rights reserved.
引用
收藏
页码:261 / 270
页数:10
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