However, DNA damage from hydroxyl radicals (24,103) and protein damage from peroxynitrite (111,112) have been found in cases of ALS. Direct oxidation of nucleosides by peroxynitrite may not be a major pathway (113). A more likely pathway for the oxidation of nucleosides is through hydroxyl radicals formed by the transitional metal (iron)-catalyzed, Haber-Weiss and Fenton-type reactions (114). This DNA damage may be related to abnormal accumulation of mitochondria in motor neurons, possibly resulting from impaired axonal transport (115) and target deprivation (116). These possible mechanisms become more plausible in light of recent findings in our laboratory with animal models.