Huntington's disease: translating a CAG repeat into a pathogenic mechanism.
The specific pattern of neuronal cell death in Huntington's disease (HD) is triggered by an abnormal version of the huntingtin protein, which is produced by translation of the HD gene defect, an expanded CAG repeat in a novel 4p16.3 gene. The extended amino-terminal polyglutamine segment may act via the protein's inherent activity, increasing it or decreasing it in a graded fashion, or, alternatively, it may confer the ability to interact with a completely different set of cellular pathways, focusing attention on the HD protein's normal and abnormal physiological functions.
MacDonald
M E
ME
Molecular Neurogenetics Unit, Massachusetts General Hospital East, Charlestown 02129, USA.
Gusella
J F
JF
D000818:Animals; D001921:Brain / Q000473:pathology*; D016923:Cell Death; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D014176:Protein Biosynthesis; D014158:Transcription, Genetic; D018911:Trinucleotide Repeats
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins