Cortical Motor Neuron Hyperexcitability and Motor Neuron Death in ALS: Dying Forward Hypothesis

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In the late 19th century, Charcot examined patients with amyotrophic lateral sclerosis (ALS) and concluded that the sclerosis in the lateral columns of the spinal cord induced the loss of neurons in the anterior horns. The reason for this remains unknown. In contrast, hyperexcitability of motor neurons is believed to be one of the pathogenetic factors for motor neuron death in ALS. In this article, I have reviewed the relationship between motor neuron hyperexcitability and motor neuron death and considered the mechanism of ALS pathogenesis.