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.
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.
Our study provides a new mechanistic link for hSOD1(G93A)-mediated impairment of LE transport to autophagy-lysosomal deficits and mitochondrial pathology.