Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.
Huntington's disease (HD) is a late-onset neurodegenerative disorder that is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (htt). The normal function of htt, and the molecular mechanisms that contribute to the disease pathogenesis, are in the process of being elucidated. In this review, we outline the potential functions of htt as defined by the proteins with which it has been found to interact. We then focus on evidence that supports a role for transcriptional dysfunction and impaired protein folding and degradation as early events in disease pathogenesis.
Landles
Christian
C
Neurogenetics Laboratory, Medical and Molecular Genetics, GKT School of Medicine, King's College London, 8th Floor Guy's Tower, Guy's Hospital, London SE1 9RT, UK. christian.landles@genetics.kcl.ac.uk
Bates
Gillian P
GP
D001343:Autophagy / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D018832:Molecular Chaperones / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D046988:Proteasome Endopeptidase Complex