The molecular basis of the selective death of motor neurons in amyotrophic lateral sclerosis (ALS) has been an enigma since its description by Charcot in 1869 Cleveland and Rothstein 2001, Julien 2001. In this issue of Neuron, Raoul et al. (2002) demonstrate a motor neuron-specific death pathway which involves Fas and NO. Remarkably, motor neurons from mice carrying ALS-linked mutant forms of superoxide dismutase 1 (SOD1) exhibit an increased sensitivity to death triggered by Fas but not other insults. These data suggest new insights into the mechanisms of, and potential therapeutic strategies for, death of motor neurons in ALS.
