Nitrotyrosination contributes minimally to toxicity of mutant SOD1 associated with ALS

Neuroreport
M M DoroudchiHeather D Durham

Abstract

Enhanced production of nitrotyrosine and subsequent protein nitration has been proposed as the mechanism by which mutant SOD1 causes death of motor neurons in a familial form of amyotrophic lateral sclerosis (FALS-1). We have tested this hypothesis in a primary culture model in which mutant human SOD1 was expressed in motor neurons of dissociated spinal cord cultures. Preventing formation of nitrotyrosine by inhibiting nitric oxide synthase rescued cultured motor neurons from excitotoxic death induced by adding glutamate to the culture medium, but failed to significantly delay death of motor neurons expressing the G93A mutant SOD1. The results do not support generation of nitrotyrosine being the predominant lethal gain of function conferred by mutations in SOD1.

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Citations

Sep 5, 2002·Journal of Neuroscience Research·Marina D KirkitadzeDavid B Teplow
Jan 25, 2003·Free Radical Biology & Medicine·Victoria C Stewart, Simon J R Heales
Feb 3, 2004·Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders : Official Publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases·Jeff Agar, Heather Durham
Mar 13, 2002·Nature Neuroscience·Jamuna R SubramaniamPhilip C Wong
Nov 21, 2001·Nature Reviews. Neuroscience·D W Cleveland, J D Rothstein

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