Our study provides a new mechanistic link for hSOD1(G93A)-mediated impairment of LE transport to autophagy-lysosomal deficits and mitochondrial pathology.
Transgenic mice expressing human Gly93 --> Ala (G93A) mutant SOD1 (mSOD1) develop severe MN disease, oxidative and nitrative damage, and mitochondrial pathology that appears to involve nitric oxide-mediated mechanisms.
G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated disease course that is associated with enhanced mitochondrial pathology and increased mitochondrial localization of mutant SOD1.