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This lecture covers motor neuron diseases, which are neurological disorders affecting the neuromuscular system, resulting in skeletal muscle paralysis with varying severity, duration, and fatality. It discusses the classification, pathological signatures, and etiology of these diseases, emphasizing the intrinsic vulnerability of motor neurons. The lecture also explores specific motor neuron diseases like Primary Lateral Sclerosis, Charcot Marie Tooth disease, and Spinal Muscular Atrophy (SMA), detailing their clinical features, genetic causes, and disease progression. Furthermore, it delves into the potential treatments for SMA, including gene therapy and splicing modifiers, highlighting the ongoing research and clinical trials in the field.