The neuromuscular junction and its glial cells as therapeutic target in ALS

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with a complex etiology. The destruction of neuromuscular junctions (NMJs) is an early event that leads to muscle weakness and paralysis due to the denervation and retraction of nerve terminals from striated muscles. Despite the importance of NMJ denervation, NMJ vulnerability and resistance remain under-characterized and the mechanisms involved ill defined. We focus on the role of Perisynaptic Schwann Cells (PSCs), glial cells at this synapse, since they regulate NMJ synaptic transmission, morphological stability and repair. I will discuss results from animal models and human analyses of the neuromuscular changes in ALS and in aging leading to NMJ denervation and instability. Strategies to use NMJs and its glial cells as therapeutic target in ALS will also be presented.