Glial mitochondropathy in infantile neuroaxonal dystrophy: pathophysiological and therapeutic implications.

Mitochondrial dysfunction is increasingly being recognized as a therapeutic target in PLA26G-associated neurodegeneration (PLAN). We demonstrated in Drosophila and in human PLA2G6 mutant fibroblasts that loss of normal PLA2G6 activity is associated with increased mitochondrial lipid peroxidation and mitochondrial dysfunction. Furthermore, we identified the therapeutic benefits of deuterated polyunsaturated fatty acids (D-PUFAs) in PLAN, through inhibition of lipid peroxidation. D-PUFAs ameliorated the locomotor deficits in flies lacking the fly orthologue of PLA2G6 (iPLA2-VIA), and reversed the mitochondrial abnormalities in patient fibroblasts harbouring pathogenic mutations in PLA2G6 (Kinghorn et al., 2015).