title: Retrograde axonal transport and motor neuron disease.
abstract: Transport of material between extensive neuronal processes and the cell body is crucial for neuronal function and survival. Growing evidence shows that deficits in axonal transport contribute to the pathogenesis of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here we review recent data indicating that defects in dynein-mediated retrograde axonal transport are involved in ALS etiology. We discuss how mutant copper-zinc superoxide dismutase (SOD1) and an aberrant interaction between mutant SOD1 and dynein could perturb retrograde transport of neurotrophic factors and mitochondria. A possible contribution of axonal transport to the aggregation and degradation processes of mutant SOD1 is also reviewed. We further consider how the interference with axonal transport and protein turnover by mutant SOD1 could influence the function and viability of motor neurons in ALS.
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, Kentucky, USA.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Ström
authors.forename: Jozsef
authors.initials: J
authors.lastname: Gal
authors.forename: Ping
authors.initials: P
authors.lastname: Shi
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Kasarskis
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Hayward
authors.forename: Haining
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism; D006801:Humans; D016472:Motor Neuron Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D009046:Motor Neurons / Q000502:physiology*; D009154:Mutation; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D004398:Dyneins