title: Impairment of SOD1-G93A motility is linked to mitochondrial movement in axons of hippocampal neurons.
abstract: Superoxide dismutase 1 (SOD1) is a well-known antioxidant enzyme. Mutation of SOD1 is closely associated with the pathogenesis of neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer's disease. However, the pathologic pathways linking neurodegenerative diseases with mutation of SOD1 remain elusive. Here, we investigated the motility of SOD1-WT and -G93A (a pathogenic mutant of SOD1), and observed correlation of axonal transport of the mutant protein with mitochondria in primary cultured hippocampal neurons. The SOD1-G93A mutant showed significant accumulation at vGlut1-positive synaptic boutons and in cell bodies, compared to SOD1-WT. The proportions of motile WT and G93A proteins were similar (~30 %) while the motility velocity of SOD1-G93A was significantly slower (~40 %) than that of the WT counterpart. This motility defect of SOD1-G93A was highly correlated with mitochondrial movement. Our results collectively suggest that the SOD1-G93A mutant has a defect in motility that is linked to mitochondrial transport in axons.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 130-701, South Korea.
authors.forename: Jae Ryul
authors.initials: JR
authors.lastname: Bae
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 130-701, South Korea. sunghyunkim@khu.ac.kr.|Department of Physiology, School of Medicine, Neurodegeneration Control Research Center, Kyung Hee University, Seoul, 130-701, South Korea. sunghyunkim@khu.ac.kr.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
keywords: Amyotrophic lateral sclerosis (ALS); Axonal transport; Mitochondrial motility; SOD1; SOD1-G93A