title: [Role of axonal transport in ALS].
abstract: Proposed hypothesis for pathomechanisms of sporadic ALS include oxidative stress, glutamate toxicity, axonal transport defects, mitochondrial impairment and so on. Although these mechanisms may be interrelated mutually, the whole picture has not been clarified. As for axonal transport defect, it is also prominently involved in the pathogenesis of many major human neurodegenerative diseases including Alzheimer's disease and Parkinson's disease, suggesting a crucial role of axonal transport in maintaining the normal neuronal function. In mutant SOD1 transgenic mice, the most popular disease model of familial ALS, the mutant SOD1 selectively associates with and damages mitochondria, leading to defect of axonal transport because of diminished ATP fuel supply for the molecular motors such as kinesin family or dynein/dynactin complex. Furthermore, the finding that mutations in the dynactin subunit p150Glued cause familial ALS demonstrates a direct role of molecular motor dysfunction and axonal transport defects in ALS. On the other hand, the mechanism of axonal transport impairment in sporadic ALS has been elusive. We have previously demonstrated that gene expression of dynactin subunit p150Glued (dynactin-1) is down-regulated in motor neurons of sporadic ALS patient from the early stage of neurodegeneration. In this article we review the role of axonal transport in the pathogenesis of ALS.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Kensuke
authors.initials: K
authors.lastname: Ikenaka
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000503:physiopathology*; D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D004195:Disease Models, Animal; D000072159:Dynactin Complex; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000032:analysis
chemical_list: C000606360:DCTN1 protein, human; C000606364:Dctn1 protein, mouse; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins