KMID : 0043320160390081144
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Archives of Pharmacal Research 2016 Volume.39 No. 8 p.1144 ~ p.1150
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Impairment of SOD1-G93A motility is linked to mitochondrial movement in axons of hippocampal neurons
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Bae Jae-Ryul
Kim Sung-Hyun
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Abstract
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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.
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KEYWORD
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SOD1, SOD1-G93A, Amyotrophic lateral sclerosis (ALS), Axonal transport, Mitochondrial motility
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