Skeletal muscle dysfunction in amyotrophic lateral sclerosis: a mitochondrial perspective and therapeutic approaches

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.

Keywords: Amyotrophic lateral sclerosis; Mitochondria; Mitochondrial transplantation; Skeletal muscle dysfunction.

Fig. 1

Mitochondrial dysfunction in ALS

Fig. 2

Skeletal muscle impairments in ALS

Fig. 3

Therapeutic approaches for ALS