Superoxide dismutase and the death of motoneurons in ALS

Amyotrophic lateral sclerosis (ALS) is a lethal disease that is characteriz ed by the relentless death of motoneurons. Mutations to Cu-Zn superoxide di smutase (SOD), though occurring in just 2-3% of individuals with ALS, remai n the only proven cause of the disease. These mutations structurally weaken SOD, which indirectly decreases its affinity for Zn. Zn-deficient SOD indu ces apoptosis in motoneurons through a mechanism involving peroxynitrite. I mportantly, Zn-deficient wild-type SOD is just as toxic as Zn-deficient ALS mutant SOD, suggesting that the loss of Zn from wild-type SOD could be inv olved in the other 98% of cases of ALS. Zn-deficient SOD could therefore be an important therapeutic target in all forms of ALS.