[Unstable expansion of CAG repeat and molecular mechanism of neurodegeneration in SCA1].
SCA1 is caused by unstable expansion of CAG repeat in the coding region of a novel gene located on chromosome 6p23. Expansion up to 40-80 repeats develop the disorder, and the repeat length correlates with age at onset, rate of progression, or clinical severity. Expanded SCA1 allele is unstable during meiosis and mitosis, which is related to anticipation phenomenon and somatic mosaicism, respectively. SCA1 gene is expressed ubiquitously. In neurons, its transcript (ataxin-1) localizes mostly in nucleus. Ataxin-1 with expanded glutamine repeat is highly ubiquinated and forms aggregation within nucleus. These findings in clinical genetical, and cell biology are all common in other polyglutamine disorders, highly indicating that common molecular mechanisms underlie in these disorders. Based on these background, recent progress in the research for SCA1 is reviewed.
Sasaki
H
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Department of Neurology, Hokkaido University School of Medicine.
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009849:Olivopontocerebellar Atrophies / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*