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Huntington’s disease: revisiting the aggregation hypothesis in polyglutamine neurodegenerative diseases
Author(s) -
Truant Ray,
Atwal Randy Singh,
Desmond Carly,
Munsie Lise,
Tran Thu
Publication year - 2008
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2008.06561.x
Subject(s) - polyglutamine tract , neurodegeneration , context (archaeology) , disease , biology , protein aggregation , huntington's disease , mutant , huntingtin , gene , genetics , medicine , paleontology , pathology
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.