Mechanisms of neuromuscular junction dysfunction in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the death of upper and lower motor neurons. Numerous studies show that structural and functional impairments of neuromuscular junctions (NMJ) occur as early as the presymptomatic stage of ALS. NMJ involvement is independent and one of the primary events in ALS pathogenesis. Aim: to review the data on characteristics and mechanisms of NMJ dysfunction at pre- and postsynaptic levels in ALS patients and a transgenic animal model of the disease. Furthermore, we report on the dysfunction of perisynaptic Schwann cells and impaired mechanisms of motor neuron and skeletal muscle interaction in ALS, with a focus on reviewed publications on targeting of molecular mechanisms underlying NMJ dysfunction and disruption in ALS. The NMJ may be a potential target for novel therapeutic approaches for ALS.