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Abstract：
Sporadic inclusion body myositis (sIBM) is a distinct subcategory of Idiopathic Inflammatory Myopathies (IIM), characterized by unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Although hyperactivation of the immune system is widely believed as the primary cause of IIM, it is debated whether non-immune tissue dysfunction might contribute to the disease\'s onset as patients with sIBM are refractory to conventional immunosuppressant treatment. Moreover, the findings that mitochondrial dysfunction can elicit non-apoptotic programmed cell death and the subsequent immune response further support this hypothesis. Notably, abnormal mitochondrial structure and activities are more prominent in the muscle of sIBM than in other types of IIM, suggesting the presence of defective mitochondria might represent an overlooked contributor to the disease onset. The large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover have provided mechanistic insights into the genesis of impaired mitochondria in sIBM. This article reviews the disease hallmarks of sIBM, the plausible contributors of mitochondrial damage in the sIBM muscle, and the immunological responses associated with mitochondrial perturbations. Additionally, the potential application of mitochondrial-targeted chemicals as a new treatment strategy to sIBM is explored and discussed.
摘要：
散发性包涵体肌炎（sIBM）是特发性炎性肌病（IIM）的一个独特的亚类，具有独特的病理特征，如肌肉炎症，有边缘的空泡,和肌纤维内的蛋白质聚集。尽管免疫系统的过度激活被广泛认为是IIM的主要原因，由于sIBM患者对常规免疫抑制剂治疗难以治疗，非免疫组织功能障碍是否可能导致疾病的发作存在争议。此外，线粒体功能障碍可以引起非凋亡性程序性细胞死亡和随后的免疫反应的发现进一步支持了这一假设。值得注意的是,异常的线粒体结构和活动在sIBM的肌肉中比在其他类型的IIM中更为突出，提示线粒体缺陷的存在可能是疾病发作的一个被忽视的因素。大规模的线粒体DNA缺失,异常蛋白质聚集，和缓慢的细胞器周转提供了对sIBM线粒体受损起源的机械见解。本文回顾了sIBM的疾病标志，sIBM肌肉线粒体损伤的可能贡献者，以及与线粒体扰动相关的免疫反应。此外,探索和讨论了线粒体靶向化学物质作为sIBM新治疗策略的潜在应用。
