More than 185 CAG repeats: a point of no return in Huntington's disease biology.

This scientific commentary discusses the biology of Huntington's disease, an autosomal dominant neurodegenerative disorder that affects motor and cognitive function. The disease is caused by inheriting a mutated version of the huntingtin (HTT) gene with more than 36-40 CAG repeats. Recent studies have linked the age of onset of Huntington's disease to the number of uninterrupted CAG repeats, suggesting that it is a DNA-related disorder. The article explores the concept of somatic repeat expansion, where additional CAG repeats accumulate over a patient's lifetime, and its role in the disease. The study by Aldous et al. investigates the threshold of CAG toxicity in the central nervous system (CNS) using a mouse model and concludes that CAG repeat lengths of 185 and above are inherently toxic and beyond the point of no return. However, the exact CAG repeat length that transitions from non-toxic to toxic in the CNS is still unknown. The article emphasizes the need for further research to define the relationship between disease progression and optimal clinical intervention strategies. [Extracted from the article]