title: [SCA6: From gene identification to recent progress on pathogenesis].
abstract: Spinocerebellar ataxia type 6 (SCA6) is one of the common dominantly inherited ataxias in Japan, featuring late-onset ataxia and selective Purkinje cell (PC) degeneration. Molecular pathogenesis of SCA6 has been attracting considerable attention since it is caused by small CAG repeat expansions within the Ca(v)2.1 voltage-gated Ca(++) channel gene (CACNA1A). During the past 9 years, efforts have been made to generate and analyze a precise SCA6 model in order to disclose its molecular pathogenesis in vivo. Evidence indicates that the SCA6 mutation does not directly change the basic properties of the channel but rather exerts neurotoxicity through a mechanism associated with age-dependent accumulation of the expanded polyglutamine protein. We envisage further analysis on a knockin model developing PC degeneration at their young age will lead to elucidation of the molecular pathways involved in SCA6 and thus be useful for developing therapeutic strategies against the disease.
authors.affiliation: Center for Brain Integration Research, Tokyo Medical and Dental University.
authors.forename: Kei
authors.initials: K
authors.lastname: Watase
authors.forename: Kinya
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics*; D020864:Calcium Channels, N-Type; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009154:Mutation; D010455:Peptides; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000473:pathology; D019680:Trinucleotide Repeat Expansion
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D010455:Peptides; C105656:CACNA1A protein, human; C097188:polyglutamine