title: [Exploration of pathogenesis-associated molecules and development of disease models for sporadic ALS].
abstract: The mechanism underlying the characteristic selective motor neuron degeneration in amyotrophic lateral sclerosis (ALS) has remained elusive. Modest advances in this research field have been achieved by the identification of copper/zinc superoxide dismutase 1 (SOD1) as one of the causative genes for rare familial ALS and by the development and analysis of mutant SOD1 transgenic animal models. However, in sporadic ALS (SALS) with many more patients, causative or critical genes situated upstream of the disease pathway have not yet been elucidated and no available disease models have been established. We have been working on screening these genes employing and combining several new technologies such as cDNA microarray, molecular indexing, and laser capture microdissection. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of SALS. Of these, in this paper, we will focus on Dorfin, a RING finger-type E3 ubiquitin ligase and dynactin1, a major component of dynein/dynactin complex that is important for retrograde axonal transport. We are now challenging creation of the disease models by simulating the gene expression changes specifically observed in SALS patients.
authors.affiliation: Department of Neurology, Nagoya University Graduate School of Medicine.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.forename: Masahiro
authors.initials: M
authors.lastname: Waza
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Niwa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D000072159:Dynactin Complex; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009154:Mutation; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D044767:Ubiquitin-Protein Ligases
chemical_list: C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C423571:RNF19A protein, human; D044767:Ubiquitin-Protein Ligases