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首页> 外文期刊>Neuropathology and applied neurobiology >Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis
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Overexpression of autophagic proteins in the skeletal muscle of sporadic inclusion body myositis

机译：散发性包涵体肌炎的骨骼肌中自噬蛋白的过表达

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Aims: Sporadic inclusion body myositis (s-IBM) is characterized by rimmed vacuole formation and misfolded protein accumulation. Intracellular protein aggregates are cleared by autophagy. When autophagy is blocked aggregates accumulate, resulting in abnormal rimmed vacuole formation. This study investigated the autophagy-lysosome pathway contribution to rimmed vacuole accumulation. Methods: Autophagy was studied in muscle biopsy specimens obtained from elevens-IBM patients, one suspected hereditary IBM patient, nine patients with other inflammatory myopathies and nine non-myopathic patients as controls. The analysis employed morphometric methods applied to immunohistochemistry using the endosome marker Clathrin, essential proteins of the autophagic cascade such as AuTophaGy-related protein ATG5, splicing variants of microtubule-associated protein light chain 3a (LC3a) and LC3b, compared with Beclin 1, the major autophagy regulator of both the initiation phase and late endosome/lysosome fusion of the autophagy-lysosome pathway. Results: In muscle biopsies of s-IBM patients, an increased expression of Clathrin, ATG5, LC3a, LC3b and Beclin 1 was shown. Moreover, the inflammatory components of the disease, essentially lymphocytes, were preferentially distributed around the Beclin 1+ myofibres. These affected myofibres also showed a moderate sarcoplasmic accumulation of SMI-31+ phospho-tau paired helical filaments. Conclusion: The overexpression of autophagy markers linked to the decreased clearance of misfolded proteins, including SMI-31, and rimmed vacuoles accumulation may exhaust cellular resources and lead to cell death.
机译：目的：散发性包涵体肌炎（s-IBM）的特征是边缘液泡形成和蛋白质积累错误。细胞内蛋白质聚集物通过自噬清除。当自噬被阻止时，聚集物会聚集，导致异常的有边缘的液泡形成。这项研究调查了自噬溶酶体途径对有缘液泡积累的贡献。方法：在自11名IBM患者，1名可疑遗传性IBM患者，9名其他炎症性肌病患者和9名非肌病患者作为对照的肌肉活检样本中研究自噬。该分析采用形态学方法，该方法使用了内体标记物Clathrin，自噬级联反应的必需蛋白（例如AuTophaGy相关蛋白ATG5），微管相关蛋白轻链3a（LC3a）和LC3b的剪接变体，与Beclin 1，自噬-溶酶体途径的起始阶段和晚期内体/溶酶体融合的主要自噬调节剂。结果：在s-IBM患者的肌肉活检中，显示网格蛋白，ATG5，LC3a，LC3b和Beclin 1的表达增加。此外，该疾病的炎性成分，主要是淋巴细胞，优先分布在Beclin 1+肌纤维周围。这些受影响的肌纤维还显示出SMI-31 +磷酸-tau配对螺旋丝的中等肌浆堆积。结论：自噬标记物的过表达与错误折叠的蛋白质（包括SMI-31）的清除率降低有关，边缘空泡的积累可能会耗尽细胞资源并导致细胞死亡。

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