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Mol. Cells 2009; 27(6): 621-627

Published online June 30, 2009

https://doi.org/10.1007/s10059-009-0095-y

© The Korean Society for Molecular and Cellular Biology

Molecular Pathogenesis of Spinocerebellar Ataxia Type 1 Disease

Seongman Kang, and Sunghoi Hong

Received: June 16, 2009; Accepted: June 19, 2009

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 ag-gregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.

Keywords aggregates, ataxin-1, cell therapy, cellular dysfunction, polyglutamine, protein interaction

Article

Minireview

Mol. Cells 2009; 27(6): 621-627

Published online June 30, 2009 https://doi.org/10.1007/s10059-009-0095-y

Copyright © The Korean Society for Molecular and Cellular Biology.

Molecular Pathogenesis of Spinocerebellar Ataxia Type 1 Disease

Seongman Kang, and Sunghoi Hong

Received: June 16, 2009; Accepted: June 19, 2009

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 ag-gregation and alleviation of the pathogenic phenotype by the application of potent inhibitors and RNA interference.

Keywords: aggregates, ataxin-1, cell therapy, cellular dysfunction, polyglutamine, protein interaction

Mol. Cells
Sep 30, 2022 Vol.45 No.9, pp. 603~672
COVER PICTURE
The Target of Rapamycin Complex (TORC) is a central regulatory hub in eukaryotes, which is well conserved in diverse plant species, including tomato (Solanum lycopersicum). Inhibition of TORC genes (SlTOR, SlLST8, and SlRAPTOR) by VIGS (virus-induced gene silencing) results in early fruit ripening in tomato. The red/ orange tomatoes are early-ripened TORC-silenced fruits, while the green tomato is a control fruit. Top, left, control fruit (TRV2-myc); top, right, TRV2-SlLST8; bottom, left, TRV2-SlTOR; bottom, right, TRV2-SlRAPTOR(Choi et al., pp. 660-672).

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