Our trails and trials in the subsarcolemmal cytoskeleton network and muscular dystrophy researches in the dystrophin era.
Our trails and trials in the subsarcolemmal cytoskeleton network and muscular dystrophy researches in the dystrophin era.
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DOI：
10.2183/pjab.86.798
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Ozawa E
中科院分区：
文献类型：
--
作者：
Ozawa E
1987年，在发现杜氏肌营养不良症（DMD）大约150年后，Kunkel克隆了其负责基因，肌营养不良蛋白基因。这是一种新物质。在克隆后的20多年里，我们对肌膜下细胞骨架网络的组成部分dystrophin以及DMD的病理机制和实验治疗的认识大大提高。在这一范式转变期间，我有幸能够作为一名活跃的研究人员在其前沿领域工作了12年。1988年我们发现肌营养不良蛋白（dystrophin）位于细胞膜上，为了研究dystrophin的功能和DMD的发病机制，我们研究了dystrophin和dystrophin-associated proteins（DAPs）复合物的结构。在这些研究的进行中，我们开始考虑抗肌萎缩蛋白-DAP复合物用于跨膜连接肌膜下细胞骨架网络和基底层以保护脂质双层。然后，我们的工作假设是，肌肉收缩时脂质双层的损伤是DMD的原因。在此过程中，我们预测，亚单位的肌聚糖（SG）复合物负责各自类型的DMD样肌营养不良症与常染色体隐性遗传。我们的预测被包括我们自己在内的许多研究人员证实是正确的。在这篇综述中，我将试图解释我们所观察到的，我们如何考虑有关的结构和功能的dystrophin-DAP复合物，和DMD和相关的肌营养不良症的病理机制。
In 1987, about 150 years after the discovery of Duchenne muscular dystrophy (DMD), its responsible gene, the dystrophin gene, was cloned by Kunkel. This was a new substance. During these 20 odd years after the cloning, our understanding on dystrophin as a component of the subsarcolemmal cytoskeleton networks and on the pathomechanisms of and experimental therapeutics for DMD has been greatly enhanced. During this paradigm change, I was fortunately able to work as an active researcher on its frontiers for 12 years. After we discovered that dystrophin is located on the cell membrane in 1988, we studied the architecture of dystrophin and dystrophin-associated proteins (DAPs) complex in order to investigate the function of dystrophin and pathomechanism of DMD. During the conduct of these studies, we came to consider that the dystrophin–DAP complex serves to transmembranously connect the subsarcolemmal cytoskeleton networks and basal lamina to protect the lipid bilayer. It then became our working hypothesis that injury of the lipid bilayer upon muscle contraction is the cause of DMD. During this process, we predicted that subunits of the sarcoglycan (SG) complex are responsible for respective types of DMD-like muscular dystrophy with autosomal recessive inheritance. Our prediction was confirmed to be true by many researchers including ourselves. In this review, I will try to explain what we observed and how we considered concerning the architecture and function of the dystrophin–DAP complex, and the pathomechanisms of DMD and related muscular dystrophies.
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DOI：
10.1016/0960-8966(91)90058-z
发表时间：
1991-01-01
期刊：
Neuromuscular disorders : NMD
影响因子：
--
作者：
Cullen, M J;Walsh, J;Worton, R G
通讯作者：
Worton, R G
影响因子：
--
作者：
CRAIG, SW;PARDO, JV
通讯作者：
PARDO, JV
影响因子：
4.8
作者：
Crosbie, RH;Heighway, J;Campbell, KP
通讯作者：
Campbell, KP
影响因子：
3.8
作者：
Ebashi, S;Endo, M
通讯作者：
Endo, M
影响因子：
7.8
作者：
Ahn, A H;Kunkel, L M
通讯作者：
Kunkel, L M