TY - JOUR T1 - Mutant Superoxide Dismutase-1-Linked Familial Amyotrophic Lateral Sclerosis: Molecular Mechanisms of Neuronal Death and Protection JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8756 LP - 8766 DO - 10.1523/JNEUROSCI.17-22-08756.1997 VL - 17 IS - 22 AU - G. D. Ghadge AU - J. P. Lee AU - V. P. Bindokas AU - J. Jordan AU - L. Ma AU - R. J. Miller AU - R. P. Roos Y1 - 1997/11/15 UR - http://www.jneurosci.org/content/17/22/8756.abstract N2 - Mutations in human Cu/Zn superoxide dismutase-1 (SOD) cause ∼20% of cases of familial amyotrophic lateral sclerosis (FALS). We investigated the mechanism of mutant SOD-induced neuronal degeneration by expressing wild-type and mutant SODs in neuronal cells by means of infection with replication-deficient recombinant adenoviruses. Expression of two FALS-related mutant SODs (A4V and V148G) caused death of differentiated PC12 cells, superior cervical ganglion neurons, and hippocampal pyramidal neurons. Cell death included many features typical of apoptosis. Death could be prevented by copper (Cu2+) chelators, Bcl-2, glutathione, vitamin E, and inhibitors of caspases. Mutant SOD-expressing PC12 cells had higher rates of superoxide (O2−) production under a variety of conditions. The results support the hypothesis that mutant SOD induced-neurodegeneration is associated with disturbances of neuronal free radical homeostasis. ER -