From Charcot to Lou Gehrig: Deciphering selective motor neuron death in ALS

Since its description by Charcot more than 130 years ago, the mechanism und erlying the characteristic selective degeneration and death of motor neuron s in amyotrophic lateral sclerosis has remained a mystery. Modern genetics has now identified mutations in two genes - SOD1 and ALS2 - as primary caus es of the disease, and has implicated others as potential contributors. Ins ights into these abnormalities, together with errors in the handling of syn aptic glutamate and the potential excitotoxic response that this alteration provokes, have provided leads for the development of new strategies to ide ntify an as yet elusive remedy for this progressive, fatal disorder.