Huntington's disease.
Huntington's disease (HD) is one of the most frequently found neurodegenerative disorders. Its main clinical manifestations are chorea, cognitive impairment and psychiatric disorders. It is an autosomal-dominant disorder with almost complete penetrance. The mutation responsible for HD, unstable expansion of a CAG repeat, is located in the 5' terminal section of the gene (IT15) that encodes huntingtin protein (Htt). The pathophysiology of HD is not entirely clear. One intriguing characteristic of HD is the special vulnerability of the striatum tomutated Htt, despite similar expression of the mutated protein in other brain regions. Aggregation of mutated Htt, transcriptional dysregulation, altered energy metabolism, excitotoxicity, impaired axonal transport and altered synaptic transmission culminate in neuronal dysfunction and death. There is currently no way of preventing or slowing down the disease progression and death usually occurs at about 20 years after diagnosis.
Roze
Emmanuel
E
UMRS 952, INSERM, UMR 7224-CNRS Université Pierre et Marie Curie-Paris-6, Paris, France. emmanuel.roze@psl.aphp.fr
Bonnet
Cecilia
C
Betuing
Sandrine
S
Caboche
Jocelyne
J
D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001479:Basal Ganglia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001692:Biological Transport / Q000235:genetics; D025063:Chromosome Disorders / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004734:Energy Metabolism / Q000235:genetics; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019680:Trinucleotide Repeat Expansion
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins