Chapter

Diseases of DNA Repair

Volume 685 of the series Advances in Experimental Medicine and Biology pp 45-63

Huntington’s Disease

  • Emmanuel RozeAffiliated withUMRS 952, INSERM UMR 7224-CNRS, Université Pierre et Marie CuriePôle des maladies du système nerveux Fédération de neurologie, Hopital Pitié-Salpétrière Email author 
  • , Cecilia BonnetAffiliated withPôle des maladies du système nerveux Fédération de neurologie, Hopital Pitié-Salpétrière
  • , Sandrine BetuingAffiliated withUMRS 952, INSERM UMR 7224-CNRS, Université Pierre et Marie Curie
  • , Jocelyne CabocheAffiliated withUMRS 952, INSERM UMR 7224-CNRS, Université Pierre et Marie Curie

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Huntington’s disease (HD) is one of the most frequently found neurodegenerative disorders. Its main clinical manifestations arc 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 repcat, is located in the 5′ tcrminal section of the gene (ITJS) 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 protcin in other brain regions. Aggregation of mutated Htt, transcriptional dysregulation, altered energy metabolism, excitotoxicity, impaired axonal transport and altered synaptic transmission culminate in neuronal dysfianction and death. There is currently no way ofpreventing or slowing down the disease progression and death usually occurs at about 20 years after dia