title: Molecular pathogenesis of spinocerebellar ataxia type 1 disease.
abstract: Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 is associated with an elongated polyglutamine tract in ataxin-1, the SCA1 gene product. As summarized in this review, recent studies have clarified the molecular mechanisms of SCA1 pathogenesis and provided direction for future therapeutic approaches. The nucleus is the subcellular site where misfolded mutant ataxin-1 acts to cause SCA1 disease in the cerebellum. The role of these nuclear aggregates is the subject of intensive study. Additional proteins have been identified, whose conformational alterations occurring through interactions with the polyglutamine tract itself or non-polyglutamine regions in ataxin-1 are the cause of SCA-1 cytotoxicity. Therapeutic hope comes from the observations concerning the reduction of nuclear aggregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.
authors: Graduate School of Life Science and Biotechnology, Korea University, Seoul 136-701, Korea.
authors: Seongman
authors: S
authors: Kang
authors: Sunghoi
authors: S
authors: Hong
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D020754:Spinocerebellar Ataxias / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; C097188:polyglutamine