Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy
Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy
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DOI：
10.1016/j.bbadis.2014.09.005
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发表时间：
2015-04-01
影响因子：
6.2
通讯作者：
Nogalska, Anna
中科院分区：
文献类型：
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作者：
Askanas, Valerie;Engel, W. King;Nogalska, Anna
散发性包涵体肌炎（s-IBM）是最常见的退行性肌肉疾病，其中衰老似乎是一个关键的危险因素。在这篇综述中，我们将重点关注s-IBM肌纤维中多蛋白聚集和积累的几种细胞分子机制及其可能的后果。这些机制包括：a)以肌肉纤维内聚集体的形式积累，几种蛋白质，包括淀粉样蛋白- β 42及其低聚物，以及以成对螺旋细丝的形式磷酸化的tau，我们认为它们可能的有害影响；b)蛋白质错误折叠和聚集，包括异常肌蛋白停滞的证据，如蛋白质转录增加，蛋白质处理不足，蛋白质翻译后修饰异常。本文还讨论了我们最近发现的异常有丝分裂的致病意义。s-IBM肌纤维与阿尔茨海默病和帕金森病（两种最常见的与衰老相关的神经退行性疾病）患者的大脑之间有趣的表型相似性也进行了讨论。这篇文章是题为“神经肌肉疾病：病理和分子发病机制”的特刊的一部分。(C) 2014年作者。Elsevier B.V.出版
Sporadic inclusion-body myositis (s-IBM) is the most common degenerative muscle disease in which aging appears to be a key risk factor. In this review we focus on several cellular molecular mechanisms responsible for multiprotein aggregation and accumulations within s-IBM muscle fibers, and their possible consequences. Those include mechanisms leading to: a) accumulation in the form of aggregates within the muscle fibers, of several proteins, including amyloid-beta 42 and its oligomers, and phosphorylated tau in the form of paired helical filaments, and we consider their putative detrimental influence; and b) protein misfolding and aggregation, including evidence of abnormal myoproteostasis, such as increased protein transcription, inadequate protein disposal, and abnormal posttranslational modifications of proteins. Pathogenic importance of our recently demonstrated abnormal mitophagy is also discussed. The intriguing phenotypic similarities between s-IBM muscle fibers and the brains of Alzheimer and Parkinson's disease patients, the two most common neurodegenerative diseases associated with aging, are also discussed. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis. (C) 2014 The Authors. Published by Elsevier B.V.