AGGREGATION OF HUNTINGTIN IN NEURONAL INTRANUCLEAR INCLUSIONS AND DYSTROPHIC NEURITES IN BRAIN

The cause of neurodegeneration in Huntington's disease (HD) is unknown . Patients with HD have an expanded NH2-terminal polyglutamine region in huntingtin. An NH2-terminal fragment of mutant huntingtin was local ized to neuronal intranuclear inclusions (NIIs) and dystrophic neurite s (DNs) in the HD cortex and striatum, which are affected in HD, and p olyglutamine length influenced the extent of huntingtin accumulation i n these structures. Ubiquitin was also found in NIIs and DNs, which su ggests that abnormal huntingtin is targeted for proteolysis but is res istant to removal. The aggregation of mutant huntingtin may be part of the pathogenic mechanism in HD.