Huntington's disease

dHuntington's disease (HD) is an autosomal dominant progressive neuropyschiatric disorder, characterized h abnormalities of movement, emotion and cognition. The most important pathologgical feature is selective neuronal loss, primarily in the striatum and cerebral cortex. HD is caused by the expansion of a CAG trinucleotide repeat in the gene encoding humingtin. The expanded repeat encodes an abnormally long polyglutamine tract, and many lines of evidence no strongly suggest that this mutation is neurotoxic. In this review, we first detail the clinical, genetic and pathological features of HID. We then describe how clues from neurotoxicological, biochemical, cell, transgenic mouse, and invertebrate models of HD lead to a multifactored model of HD pathogenesis,. We Conclude h discussing how the model of HD serves as a guide to the development of rational therapeutics for this devastating disease. (C) 2001 Association for Research in Nervous and Mental Disease. All rights reserved.