Recent advances in understanding the pathogenesis of Huntington's disease

Huntington's disease (HD) is an autosomal, dominantly inherited neurodegene rative disorder that is characterized by abnormal involuntary. movements (c horea), intellectual impairment and selective neuronal loss. The expansion of a polymorphic trinucleotide repeat (the sequence CAG that codes for glut amine) to a length that exceeds 40 repeat units in exon I of the gene, HD, correlates with the onset and progression of the disease. The protein encod ed by HD, huntingtin, is normally localized in the cytoplasm, whereas the m utant protein is also found in the nucleus, suggesting that its translocati on to this site is important for the pathogenesis of HD. Although several p roteins that interact with huntingtin have been identified in vitro, the si gnificance of these interactions with the mutant protein in the pathogenesi s of HD has yet to be determined. Recent progress in the development of cel lular and animal models for the disease have provided invaluable insights a nd resources for studying the disease mechanisms underlying HD, and will be useful for screening and evaluating possible therapeutic strategies.