title: [Exploration of pathogenesis and therapy development for ALS employing sporadic disease model].
abstract: The mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remain poorly understood even now 140 years after the first description of the disease in 1869 by Jean-Martin Charcot. Exploration of pathogenesis of ALS has long been dependent on transgenic animal models with mutations in the copper/ zinc superoxide dismutase 1 (SOD1) gene. However, the lack of therapeutic concordance between these animal models and human sporadic ALS patients is troubling. The reasons include that there might exist the differences of pathogenesis between sporadic and familial ALS and/or the disease models for sporadic ALS have not been established. We have been working on screening motor neuron-specific genes critical for pathogenesis of sporadic ALS using cDNA microarray and laser capture microdissection techniques. Many of the resultant genes are of intense interest and may provide a powerful tool for determining the molecular mechanisms of sporadic ALS. In particular, dynactin-1, a major component of dynein/dynactin complex and several cell cycle-related genes are the targets of our research. Development and analysis of new disease models for sporadic ALS based on these genes will open an avenue for novel therapeutics.
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: Masahiko
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Gen
authors.initials: G
authors.lastname: Sobue
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000628:therapy*; D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D056745:Cyclin C; D004195:Disease Models, Animal; D000072159:Dynactin Complex; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D056745:Cyclin C; C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins