| Type: | Family | Name: | Huntingtin |
| Description: | Huntington's disease (HD) is a mid-life onset, inherited, neurodegenerative disorder characterised by motor impairment, involuntary movements (chorea),psychiatric disorders and dementia []. The disease results from theexpansion of a polyglutamine-encoding CAG repeat in a gene of unknown function. Moderate expansion of glutamine-coding CAG repeats has beenfound in other neurological diseases (e.g. spinobulbar muscular atrophy and Machado-Joseph disease), in all of which the pathological mechanismlinked to the expansion of the polyglutamine tract in the protein remains a mystery.The HD transcript is highly conserved, significant differences, as already noted, occurring in the N-terminal Gln-repeat region. Huntingtin normallycontains 10-35 repeats, but shows 36-120 repeats in the disease form. Migration differences between normal and mutated huntingtin in a denaturingpolyacrylamide gel suggest that the poly-Gln stretch disrupts the protein conformation. This finding is consistent with the observation thatGln repeats may form tightly-linked beta-sheets that could act as polar zippers []. It has been shown that neuronal inclusions of patients with Huntington's disease contains a broad range of N-terminal fragments of expanded huntingtin and insoluble polymers []. The polymerisation of the monomeric huntingtin bearing a polyglutamine expansion is selectively produced by transglutaminase [, ]. | Short Name: | Huntingtin |
