Ochala Julien
Department of Neuroscience, Clinical Neurophysiology, University Hospital, Entrance 85, SE-751 85, Uppsala, Sweden.
J Mol Med (Berl). 2008 Nov;86(11):1197-204. doi: 10.1007/s00109-008-0380-9. Epub 2008 Jun 24.
In humans, more than 140 different mutations within seven genes (ACTA1, TPM2, TPM3, TNNI2, TNNT1, TNNT3, and NEB) that encode thin filament proteins (skeletal alpha-actin, beta-tropomyosin, gamma-tropomyosin, fast skeletal muscle troponin I, slow skeletal muscle troponin T, fast skeletal muscle troponin T, and nebulin, respectively) have been identified. These mutations have been linked to muscle weakness and various congenital skeletal myopathies including nemaline myopathy, distal arthrogryposis, cap disease, actin myopathy, congenital fiber type disproportion, rod-core myopathy, intranuclear rod myopathy, and distal myopathy, with a dramatic negative impact on the quality of life. In this review, we discuss studies that use various approaches such as patient biopsy specimen samples, tissue culture systems or transgenic animal models, and that demonstrate how thin filament proteins mutations alter muscle structure and contractile function. With an enhanced understanding of the cellular and molecular mechanisms underlying muscle weakness in patients carrying such mutations, better therapy strategies can be developed to improve the quality of life.
在人类中，已鉴定出七个基因（ACTA1、TPM2、TPM3、TNNI2、TNNT1、TNNT3和NEB）内有140多种不同突变，这些基因分别编码细肌丝蛋白（骨骼肌α-肌动蛋白、β-原肌球蛋白、γ-原肌球蛋白、快肌型骨骼肌肌钙蛋白I、慢肌型骨骼肌肌钙蛋白T、快肌型骨骼肌肌钙蛋白T和伴肌动蛋白）。这些突变与肌无力以及各种先天性骨骼肌病相关，包括杆状体肌病、远端关节弯曲综合征、帽状病、肌动蛋白肌病、先天性纤维类型不均衡、杆状核肌病、核内杆状肌病和远端肌病，对生活质量有巨大负面影响。在本综述中，我们讨论了使用多种方法（如患者活检标本、组织培养系统或转基因动物模型）的研究，这些研究表明细肌丝蛋白突变如何改变肌肉结构和收缩功能。随着对携带此类突变患者肌无力背后的细胞和分子机制的深入了解，可以制定更好的治疗策略来提高生活质量。
