Protein Kinase C Is a Key Target for Attenuation of Leigh Syndrome by Rapamycin

In a study from 2019, researchers investigated the effects of rapamycin, an mTOR inhibitor, on Leigh syndrome, a fatal neurometabolic disorder, using a mouse model (Ndufs4 KO mice). They analyzed changes in the brain proteome and phosphoproteome after rapamycin treatment and found that it not only altered mitochondrial structure and inhibited signaling through mTOR complexes but also inhibited multiple protein kinase C (PKC) isoforms. The study demonstrated that administering PKC inhibitors increased survival, delayed neurological deficits, and prevented hair loss in the Ndufs4 KO mice, suggesting that PKC is a promising therapeutic target for treating severe mitochondrial diseases like Leigh syndrome.