Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential.
Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential.
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ALS中的缺乏肌膜修复：具有治疗潜力的新型机制。
DOI：
10.3390/cells11203263
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发表时间：
2022-10-17
期刊：
影响因子：
6
通讯作者：
Zhou, Jingsong
中科院分区：
文献类型：
--
作者：
Li, Ang;Yi, Jianxun;Li, Xuejun;Dong, Li;Ostrow, Lyle W.;Ma, Jianjie;Zhou, Jingsong
骨骼肌肌纤维的质膜（肌膜）在正常日常运动期间和/或在疾病条件下易受由物理和化学应力引起的损伤。这些急性质膜破坏通常由内在膜再密封过程补偿，该过程涉及多种细胞内蛋白质的相互作用，包括dysferlin、膜联蛋白、小窝蛋白和Mitsugumin 53（MG 53）/TRIM 72。有新的证据表明肌萎缩侧索硬化症（ALS）中受损的肌肉肌膜修复机制。神经肌肉接头（NMJ）附近的线粒体功能障碍增加了氧化应激，引发MG 53聚集和功能丧失。受损的膜修复进一步破坏了肌膜的脆弱性，并在恶性循环中放大了氧化应激。本文回顾了现有文献，支持ALS是一种氧化应激诱导的肌膜修复中断的疾病，损害了NMJ的完整性，因此增强肌膜修复机制可能是ALS的一种可行的治疗策略。
The plasma membrane (sarcolemma) of skeletal muscle myofibers is susceptible to injury caused by physical and chemical stresses during normal daily movement and/or under disease conditions. These acute plasma membrane disruptions are normally compensated by an intrinsic membrane resealing process involving interactions of multiple intracellular proteins including dysferlin, annexin, caveolin, and Mitsugumin 53 (MG53)/TRIM72. There is new evidence for compromised muscle sarcolemma repair mechanisms in Amyotrophic Lateral Sclerosis (ALS). Mitochondrial dysfunction in proximity to neuromuscular junctions (NMJs) increases oxidative stress, triggering MG53 aggregation and loss of its function. Compromised membrane repair further worsens sarcolemma fragility and amplifies oxidative stress in a vicious cycle. This article is to review existing literature supporting the concept that ALS is a disease of oxidative-stress induced disruption of muscle membrane repair that compromise the integrity of the NMJs and hence augmenting muscle membrane repair mechanisms could represent a viable therapeutic strategy for ALS.
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影响因子：
7.4
作者：
D'Amico, Emanuele;Factor-Litvak, Pam;Santella, Regina M.;Mitsumoto, Hiroshi
通讯作者：
Mitsumoto, Hiroshi
影响因子：
17.1
作者：
Duann P;Li H;Lin P;Tan T;Wang Z;Chen K;Zhou X;Gumpper K;Zhu H;Ludwig T;Mohler PJ;Rovin B;Abraham WT;Zeng C;Ma J
通讯作者：
Ma J
影响因子：
7.8
作者：
Dobrowolny, Gabriella;Giacinti, Cristina;Pelosi, Laura;Nicoletti, Carmine;Winn, Nadine;Barberi, Laura;Molinaro, Mario;Rosenthal, Nadia;Musaro, Antonio
通讯作者：
Musaro, Antonio
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
3.7
作者：
Dupuis L;Gonzalez de Aguilar JL;Echaniz-Laguna A;Eschbach J;Rene F;Oudart H;Halter B;Huze C;Schaeffer L;Bouillaud F;Loeffler JP
通讯作者：
Loeffler JP