Molecules and Cells

, Volume 27, Issue 6, pp 621–627

Molecular pathogenesis of spinocerebellar ataxia type 1 disease

Minireview

DOI: 10.1007/s10059-009-0095-y

Cite this article as:
Kang, S. & Hong, S. Mol Cells (2009) 27: 621. doi:10.1007/s10059-009-0095-y

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.

Keywords

aggregatesataxin-1cell therapycellular dysfunctionpolyglutamineprotein interaction

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2009

Authors and Affiliations

  1. 1.Graduate School of Life Science and BiotechnologyKorea UniversitySeoulKorea
  2. 2.Department of Clinical Laboratory Science, College of Health ScienceKorea UniversitySeoulKorea