Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 17, 2022
- Source ID
- 10.3390/cells11203263
Entities
People
- Ang Li
- Dong Li
- Jianjie Ma
- Jianxun Yi
- Jingsong Zhou
- Lyle W. Ostrow
- Xuejun Li
Organizations
- ALS Association
- Istituto Superiore di SanitÃ
- Target ALS
- United States Department of Defense