title: Huntington's disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases.
abstract: After the successful cloning of the first gene for a polyglutamine disease in 1991, the expanded polyglutamine tract in the nine polyglutamine disease proteins became an obvious therapeutic target. Early hypotheses were that misfolded, precipitated protein could be a universal pathogenic mechanism. However, new data are accumulating on Huntington's disease and other polyglutamine diseases that appear to contradict the toxic aggregate hypothesis. Recent data suggest that the toxic species of protein in these diseases may be soluble mutant conformers, and that the protein context of expanded polyglutamine is critical to understanding disease specificity. Here we discuss recent publications that define other important therapeutic targets for polyglutamine-mediated neurodegeneration related to the context of the expanded polyglutamine tract in the disease protein.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada. truantr@mcmaster.ca
authors.forename: Ray
authors.initials: R
authors.lastname: Truant
authors.forename: Randy Singh
authors.initials: RS
authors.lastname: Atwal
authors.forename: Carly
authors.initials: C
authors.lastname: Desmond
authors.forename: Lise
authors.initials: L
authors.lastname: Munsie
authors.forename: Thu
authors.initials: T
authors.lastname: Tran
mesh_terms: D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology*; D008962:Models, Theoretical; D010455:Peptides / Q000235:genetics
chemical_list: D010455:Peptides; C097188:polyglutamine