Mol. Cells 2009; 27(6): 621-627
Published online June 22, 2009
https://doi.org/10.1007/s10059-009-0095-y
© The Korean Society for Molecular and Cellular Biology
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 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.
Seongman Kang, and Sunghoi Hong
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
Jae Woo Shin, Seungwon Ryu, Jongho Ham, Keehoon Jung, Sangho Lee, Doo Hyun Chung, Hye-Ryun Kang, and Hye Young Kim
Mol. Cells 2021; 44(8): 580-590 https://doi.org/10.14348/molcells.2021.0101Dong-Sik Chae, Seongho Han, Min-Kyung Lee, and Sung-Whan Kim
Mol. Cells 2021; 44(4): 245-253 https://doi.org/10.14348/molcells.2021.0037Tiffany W. Todd, and Janghoo Lim
Mol. Cells 2013; 36(3): 185-194 https://doi.org/10.1007/s10059-013-0167-x