Non-coding RNAs in polyglutamine disorders: friend or foe?

摘要

Polyglutamine (polyQ) disorders constitute a family of devastating, dominantly inherited neurodegenerative conditions caused due to dynamic mutation involving the expansion of CAG triplet repeats in the coding region. A common feature of polyQ disorders is that they become clinically evident only late in life - sometimes in the fourth decade or later. Subsequent to the onset, the symptoms of the disorder may worsen over the next 10-20 years as the affected neurons degenerate and finally die (Zoghbi and Orr 2000; Siwach and Ganesh 2008). Till date, ten such neurodegenerative disorders known to be caused by expansion of the CAG repeat in the coding region of the respective genes have been identified (Siwach and Ganesh 2008). PolyQ disorders include Huntington disease (HD), six distinct forms of spinocerebellar ataxia (SCA-1, 2, 3, 6, 7 and 17), dentatorubropallidoluysian atrophy (DRPLA) and spinobulbar muscular atrophy (SBMA) (reviewed in Bates 2005; Gatchel and Zoghbi 2005). Barring SBMA, which is X-linked, all other polyQ disorders are autosomal dominant in inheritance {see Gatchel and Zoghbi 2005; Siwach and Ganesh 2008). A pathological hallmark of polyQ disorders is the presence of intracellular protein aggregates in the neurons of affected patients, in cell culture models and in mouse and fly models (DiFiglia et al 1997; Davies et al 1997; Warrick et al 1998; Kim et al 2002).