TRIM proteins in therapeutic membrane repair of muscular dystrophy.
TRIM proteins in therapeutic membrane repair of muscular dystrophy.
复制标题
DOI：
10.1001/jamaneurol.2013.469
复制
发表时间：
2013-07
期刊：
影响因子：
29
通讯作者：
Weisleder, Noah
中科院分区：
文献类型：
--
作者：
Alloush, Jenna;Weisleder, Noah
肌营养不良代表了一个主要的未满足的医疗需求，因为只有姑息治疗存在这些衰弱的疾病。由于多种形式的肌营养不良症是由受损的肌膜完整性引起的，因此可以靶向这种膜屏障功能丧失的治疗方法可以适用于许多这些不同的遗传疾病。一种提供了影响受损膜完整性的极好机会的途径是细胞用于修复质膜损伤的过程。膜修复是一种保守的途径，其中许多不同细胞类型的质膜中的破坏通过胞内囊泡运输到损伤部位而重新密封，在损伤部位这些囊泡可以融合并修补膜破坏。最近在骨骼肌中发现了与该过程相关的多个基因，这为靶向该机制以增加膜修复作为治疗肌营养不良症的疗法提供了机会。一个这样的基因是蛋白质的三部分基序（TRIM）家族的成员，mitsugumin 53（MG 53）或TRIM 72，其是横纹肌中膜修复途径的重要组分。最近的结果表明，MG 53/TRIM 72蛋白可以直接用作治疗剂，以增加许多细胞类型的膜修复能力，并治疗肌营养不良症小鼠模型中的某些病理学方面。重组人（rhMG 53）在肌营养不良症和其他疾病的治疗中有很大的潜力，其中受损的膜完整性有助于疾病的进展。其他TRIM家族蛋白可能为类似疾病状态的治疗干预提供额外的靶点。
Muscular dystrophy represents a major unmet medical need as only palliative treatments exist for these debilitating diseases. Since multiple forms of muscular dystrophy arise from compromised sarcolemmal membrane integrity a therapeutic approach that can target this loss of membrane barrier function could be applicable to a number of these distinct genetic diseases. One pathway that presents an excellent opportunity to affect compromised membrane integrity is the process that the cell uses to repair injuries to the plasma membrane. Membrane repair is a conserved pathway where disruptions in the plasma membrane of many different cell types are resealed by trafficking of intracellular vesicles to the injury site where these vesicles can fuse and patch the membrane disruption. Recent discoveries of multiple genes associated with this process in skeletal muscle provide opportunities to target this mechanism to increase membrane repair as a therapy to treat muscular dystrophy. One such gene is a member of the tripartite motif (TRIM) family of proteins, mitsugumin 53 (MG53) or TRIM72, that is an essential component of the membrane repair pathway in striated muscles. Recent results indicate that MG53/TRIM72 protein can be directly applied as a therapeutic agent to increase membrane repair capacity of many cell types and treat some aspects of the pathology in mouse models of muscular dystrophy. There is great potential for the use of recombinant human (rhMG53) in the treatment of muscular dystrophy and other diseases where compromised membrane integrity contributes to the progression of the disease. Other TRIM family proteins may provide additional targets for therapeutic intervention in similar disease states.
登录
查看更多内容
影响因子：
17.1
作者：
Weisleder N;Takizawa N;Lin P;Wang X;Cao C;Zhang Y;Tan T;Ferrante C;Zhu H;Chen PJ;Yan R;Sterling M;Zhao X;Hwang M;Takeshima M;Cai C;Cheng H;Takeshima H;Xiao RP;Ma J
通讯作者：
Ma J
DOI：
10.1083/jcb.131.6.1747
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bi GQ;Alderton JM;Steinhardt RA
通讯作者：
Steinhardt RA
影响因子：
21.3
作者：
Cai, Chuanxi;Masumiya, Haruko;Weisleder, Noah;Matsuda, Noriyuki;Nishi, Miyuki;Hwang, Moonsun;Ko, Jae-Kyun;Lin, Peihui;Thornton, Angela;Zhao, Xiaoli;Pan, Zui;Komazaki, Shinji;Brotto, Marco;Takeshima, Hiroshi;Ma, Jianjie
通讯作者：
Ma, Jianjie
影响因子：
12.4
作者：
He, Bo;Tang, Ru-hang;Xiao, Xiao
通讯作者：
Xiao, Xiao
影响因子：
12.4
作者：
Lee, C. S.;Yi, J-S;Ko, Y-G
通讯作者：
Ko, Y-G