Molecular pathogenesis of spinocerebellar ataxia type 1 disease

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)621-627
Number of pages7
JournalMolecules and Cells
Volume27
Issue number6
DOIs
Publication statusPublished - 2009 Jul 17

Fingerprint

Spinocerebellar Ataxias
Cerebellar Diseases
Ataxia
RNA Interference
Neurodegenerative Diseases
Phenotype
Therapeutics
Genes
Ataxin-1
Proteins

Keywords

  • Aggregates
  • Ataxin-1
  • Cell therapy
  • Cellular dysfunction
  • Polyglutamine
  • Protein interaction

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Molecular pathogenesis of spinocerebellar ataxia type 1 disease. / Kang, Seong Man; Hong, Sunghoi.

In: Molecules and Cells, Vol. 27, No. 6, 17.07.2009, p. 621-627.

Research output: Contribution to journalArticle

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