Nitrotyrosination contributes minimally to toxicity of mutant SOD1 associated with ALS

Enhanced production of nitrotyrosine and subsequent protein nitration has b een proposed as the mechanism by which mutant SODI causes death of motor ne urons in a familiar form of amyotrophic lateral sclerosis (FALS-I). We have tested this hypothesis in a primary culture model in which mutant human SO DI was expressed in motor neurons of dissociated spinal cord cultures. Prev enting formation of nitrotyrosine by inhibiting nitric oxide synthase rescu ed cultured motor neurons from excitotoxic death induced by adding glutamat e to the culture medium, but failed to significantly delay death of motor n eurons expressing the G93A mutant SODI. The results do not support generati on of nitrotyrosine being the predominant lethal gain of function conferred by mutations in SODI. NeuroReport 12: 1243-1243 (C) 2001 Lippincott Willia ms & Wilkins.