Abstract Introduction Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease that leads to the breakdown of motor neurons in the brain and spinal cord. This degeneration disrupts neuromuscular communication, causing muscle weakness, atrophy, and eventual loss of voluntary movement. The Neuromuscular Junction (NMJ), a critical site for neural impulse transmission, plays a key role in motor control. Emerging evidence suggests that Muscle-specific Kinase (MuSK), a protein essential for NMJ stability, may be implicated in ALS pathology, with its dysfunction potentially accelerating motor neuron degeneration. Short summary Research indicates that MuSK dysfunction at the NMJ impairs neuromuscular signalling in ALS. Clinical studies have shown defects in the AGRN-MUSK pathway in ALS patients, suggesting its involvement in disease progression. Preclinical studies using SOD1-G93A mouse models further support this link, demonstrating that MuSK-targeted therapies improve motor responses, prolong survival, and enhance neuromuscular function. These findings highlight MuSK’s essential role in NMJ integrity and its potential as a therapeutic target for ALS treatment. Conclusion Current evidence underscores the crucial role of MuSK in NMJ maintenance, a function compromised in ALS. Therapeutic strategies to restore or enhance MuSK signalling hold promise for slowing disease progression and preserving motor function. Future research should focus on elucidating the molecular mechanisms underlying MuSK dysfunction in ALS and developing targeted interventions that optimize its therapeutic potential.
Gautam et al. (Mon,) studied this question.