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Model of mitochondrial dynamics impairment in SOD1-fALS. Mutant SOD1 causes impairment of mitochondrial dynamics, by affecting fusion and fission and transport. In ALS motor neurons, mitochondria become smaller and dysfunctional, and therefore, ATP supply is reduced, and Ca2+ buffering impaired at synapses. As a consequence, synapses are lost, and a dying-back process in the axon is initiated, which leads to a progressive distal axonopathy. NMJ, neuromuscular junction.
