title: Polyglutamine neurodegeneration: expanded glutamines enhance native functions.
abstract: An intriguing set of neurodegenerative disease are the nine disorders caused by the expansion of a unstable trinucleotide CAG repeat where the repeat is located within the coding of the affected gene, that is, the polyglutamine (polyQ) diseases. A gain-of-function mechanism for toxicity in polyQ diseases is widely thought to have a major role in pathogenesis. Yet, the specific nature of this gain-of-function is a matter of considerable discussion. The basic issue concerns whether toxicity stems from the native or normal function of the affected protein versus a novel function induced by polyQ expansion. For at least three of the polyQ disease considerable evidence is accumulating that pathology is mediated by a polyQ-induced exaggeration of a native function of the host protein.
authors.affiliation: Institute for Translational Neuroscience, Department of laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA. orrxx002@umn.edu
authors.forename: Harry T
authors.initials: HT
authors.lastname: Orr
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D005973:Glutamine / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020754:Spinocerebellar Ataxias / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D019680:Trinucleotide Repeat Expansion
chemical_list: C410798:AR protein, human; D001324:Autoantigens; D018797:Cell Cycle Proteins; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; C086074:PCM1 protein, human; D010455:Peptides; D011944:Receptors, Androgen; D005973:Glutamine; C097188:polyglutamine