Immune-mediated mechanisms potentially regulate the disease time-course of duchenne muscular dystrophy and provide targets for therapeutic intervention.
Immune-mediated mechanisms potentially regulate the disease time-course of duchenne muscular dystrophy and provide targets for therapeutic intervention.
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DOI：
10.1016/j.pmrj.2009.04.010
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发表时间：
2009-08
期刊：
影响因子：
2.1
通讯作者：
Grange, Robert W.
中科院分区：
文献类型：
--
作者：
Evans, Nicholas P.;Misyak, Sarah A.;Robertson, John L.;Bassaganya-Riera, Josep;Grange, Robert W.
杜氏肌营养不良症是一种致命的肌肉萎缩性疾病，影响男孩。肌营养不良蛋白基因的突变导致肌质膜上缺乏肌营养不良蛋白糖蛋白复合物（DGC）。在健康的肌纤维中，DGC在细胞外基质和细胞骨架之间形成联系，以防止收缩诱导的膜损伤并调节细胞信号传导。DGC的缺乏导致炎症信号级联的异常调节。炎症是营养不良性肌肉病变形成的关键病理特征，但该过程在疾病时程中的作用和调节尚未得到充分研究。转录因子NF-κB已被证明有助于疾病过程，并可能与营养不良肌肉中观察到的炎性基因表达增加有关，包括细胞因子和趋化因子。这些异常的信号传导过程可以调节导致疾病发作的炎症事件的早期时间进程。这篇综述批判性地评估了DMD患者和mdx小鼠的营养不良性肌肉病变是由炎症信号调节的免疫介导机制的结果的可能性，并强调了新的治疗方向。
Duchenne muscular dystrophy is a lethal muscle wasting disease that affects boys. Mutations in the dystrophin gene result in the absence of the dystrophin glycoprotein complex (DGC) from muscle plasma membranes. In healthy muscle fibers, the DGC forms a link between the extracellular matrix and the cytoskeleton to protect against contraction-induced membrane lesions and to regulate cell signaling. The absence of the DGC results in aberrant regulation of inflammatory signaling cascades. Inflammation is a key pathological characteristic of dystrophic muscle lesion formation, but the role and regulation of this process in the disease time course has not been sufficiently examined. The transcription factor, NF-κB has been shown to contribute to the disease process and is likely involved with increased inflammatory gene expression, including cytokines and chemokines, seen in dystrophic muscle. These aberrant signaling processes may regulate the early time course of inflammatory events that contribute to disease onset. This review critically evaluates the possibility that dystrophic muscle lesions in both DMD patients and mdx mice are the result of immune-mediated mechanisms that are regulated by inflammatory signaling and also highlights new therapeutic directions.
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