How does the Huntington's disease mutation damage cells?
Huntington's Disease (HD) is an autosomal dominant neurodegenerative condition with devastating consequences. HD is caused by the expansion of a CAG trinucleotide repeat stretch in the coding sequence of the HD gene that gives rise to a long polyglutamine tract in the huntingtin protein. How this mutated protein gives rise to the disease state is controversial. In this Perspective, I discuss the results of a new study on the effects of the mutated huntingtin protein in light of previous findings and suggest that the HD mutation damages cells by perturbing multiple parallel pathways by gain-of-function and possibly also dominant negative mechanisms.
D000818:Animals; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018911:Trinucleotide Repeats / Q000235:genetics
C086055:HTT protein, human; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins