Newest pathogenetic considerations in inclusion-body myositis: possible role of amyloid-beta, cholesterol, relation to aging and to Alzheimer's disease.
Newest pathogenetic considerations in inclusion-body myositis: possible role of amyloid-beta, cholesterol, relation to aging and to Alzheimer's disease.
复制标题
DOI：
10.1007/s11926-002-0088-8
复制
发表时间：
2002-10-01
影响因子：
5
通讯作者：
Engel, W King
中科院分区：
文献类型：
--
作者：
Askanas, Valerie;Engel, W King
本报告总结了散发性包涵体肌炎的临床特征和诊断标准，以及寻找散发性包涵体肌炎致病机制的最新进展。根据作者的研究，有几个过程似乎与仍推测的发病机制相关很重要：淀粉样蛋白-b 前体蛋白的转录和积累增加以及其蛋白水解片段淀粉样蛋白-b 的积累；与脂质代谢相关的成分（如低密度脂蛋白受体和胆固醇）异常蓄积，胆固醇蓄积可能是其异常运输造成的；氧化应激；其他阿尔茨海默病相关蛋白的积累，包括磷酸化 tau 蛋白；这些变化发生的肌肉细胞老化的环境。作者的基本假设是，衰老肌纤维内淀粉样蛋白-b 前体蛋白的过度表达是导致随后致病级联的早期上游事件。讨论了包涵体肌炎肌肉和阿尔茨海默氏病大脑之间显着的病理相似性。
This report summarizes clinical features and diagnostic criteria, and the newest advances related to seeking the pathogenic mechanism(s) of sporadic inclusion-body myositis. On the basis of the authors' research, several processes seem to be important in relation to the still-speculative pathogenesis: increased transcription and accumulation of amyloid-b precursor protein and accumulation of its proteolytic fragment amyloid-b; abnormal accumulation of components related to lipid metabolism (eg, low-density lipoprotein receptors and cholesterol; accumulation of cholesterol is possibly caused by its abnormal trafficking); oxidative stress; accumulations of other Alzheimer-related proteins including phosphorylated tau; a milieu of muscle cellular aging in which these changes occur. The authors' basic hypothesis is that overexpression of amyloid-b precursor protein within the aging muscle fibers is an early upstream event causing the subsequent pathogenic cascade. The remarkable pathologic similarities between inclusion-body myositis muscle and Alzheimer's disease brain are discussed.