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polyglutamine repeat diseases

Wednesday 16 July 2003


- Huntington disease (huntingtin)
- spinocerebellar ataxias

  • SCA1 (ataxin-1)
  • SCA2 (ataxin-2)
  • SCA3 (ataxin-3)
  • SCA6 (CACNA1A)
  • SCA7 (ataxin-7)
  • SCA17 (TAT-BP)

- dentatorubral pallidoluysian atrophy (DRPLA) (atrophin-1)
- spinobulbar muscular atrophy (SBMA) (AR androgen receptor)


Expansion of CAG trinucleotide repeats coding for polyglutamine in unrelated proteins causes at least nine late-onset progressive neurodegenerative disorders, including Huntington’s disease and a number of spinocerebellar ataxias.

Expanded polyglutamine provokes a dominant gain-of-function neurotoxicity, regardless of the specific protein context within which it resides.

Nevertheless, the protein context does modulate polyglutamine toxicity, as evidenced by the distinct clinical and pathological features of the various disorders.

Importantly, polyglutamine toxicity might derive from its ability to aggregate. Indeed, aggregation probably underlies some defining - attributes of the polyglutamine disorders, such as their late onset, progressive nature, and the dependence of onset age on polyglutamine length.


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