Inclusion-body myositis -: A myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition
Inclusion-body myositis -: A myodegenerative conformational disorder associated with Aβ, protein misfolding, and proteasome inhibition
复制标题
DOI：
10.1212/01.wnl.0000192128.13875.1e
复制
发表时间：
2006-01-01
期刊：
影响因子：
9.9
通讯作者：
Engel, WK
中科院分区：
文献类型：
--
作者：
Askanas, V;Engel, WK
散发性包涵体肌炎（s-IBM）是老年人最常见的肌肉疾病，原因不明，没有成功的治疗方法。我们总结了我们最近的发现，这提供了一个更好的理解在致病级联的步骤。我们认为s-IBM主要是一种肌退行性疾病。有趣的是s-IBM肌纤维和老年痴呆症（老年人最常见的神经退行性疾病）的大脑之间的表型相似性。在s-IBM中，淀粉样蛋白- β (A β)前体蛋白及其蛋白水解片段A β的异常积累，与肌纤维的细胞内环境老化有关，似乎是关键的上游致病事件。我们认为，蛋白质的异常积累、错误折叠和聚集，可能是由衰老环境引起的，并由氧化应激加剧，导致s- ibm特异性空泡变性和肌肉纤维萎缩。
Sporadic inclusion-body myositis (s-IBM), the most common muscle disease of older persons, is of unknown cause and there is no successful treatment. We summarize our most recent findings, which provide a better understanding of the steps in the pathogenetic cascade. We suggest that s-IBM is primarily a myodegenerative disease. Intriguing are the phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer disease, the most common neurodegenerative disease of older persons. In s-IBM, abnormal accumulation of the amyloid-beta (A beta) precursor protein and its proteolytic fragment, A beta, associated with the aging intracellular milieu of the muscle fiber, appear to be key upstream pathogenic events. We propose that the identified abnormal accumulation, misfolding, and aggregation of proteins, perhaps provoked by the aging milieu and aggravated by the oxidative stress, lead to the s-IBM-specific vacuolar degeneration and atrophy of muscle fibers.