The Mechanisms of Nuclear Proteotoxicity in Polyglutamine Spinocerebellar Ataxias

Davin Lee, Yun Il Lee, Young Sam Lee, Sung Bae Lee

Research output: Contribution to journalReview articlepeer-review


Polyglutamine (polyQ) spinocerebellar ataxias (SCAs) are the most prevalent subset of SCAs and share the aberrant expansion of Q-encoding CAG repeats within the coding sequences of disease-responsible genes as their common genetic cause. These polyQ SCAs (SCA1, SCA2, SCA3, SCA6, SCA7, and SCA17) are inherited neurodegenerative diseases characterized by the progressive atrophy of the cerebellum and connected regions of the nervous system, which leads to loss of fine muscle movement coordination. Upon the expansion of polyQ repeats, the mutated proteins typically accumulate disproportionately in the neuronal nucleus, where they sequester various target molecules, including transcription factors and other nuclear proteins. However, it is not yet clearly understood how CAG repeat expansion takes place or how expanded polyQ proteins accumulate in the nucleus. In this article, we review the current knowledge on the molecular and cellular bases of nuclear proteotoxicity of polyQ proteins in SCAs and present our perspectives on the remaining issues surrounding these diseases.

Original languageEnglish (US)
Article number489
JournalFrontiers in Neuroscience
StatePublished - Jun 4 2020
Externally publishedYes


  • CAG repeat expansion
  • nuclear proteotoxicity
  • nuclear translocation
  • polyQ SCAs
  • repeat instability

ASJC Scopus subject areas

  • General Neuroscience


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