Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease

Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10671-6. doi: 10.1073/pnas.162362299. Epub 2002 Jul 29.


Huntington's disease (HD) is an untreatable neurological disorder caused by selective and progressive degeneration of the caudate nucleus and putamen of the basal ganglia. Although the etiology of HD pathology is not fully understood, the observed loss of neuronal cells is thought to occur primarily through apoptosis. Furthermore, there is evidence in HD that cell death is mediated through mitochondrial pathways, and mitochondrial deficits are commonly associated with HD. We have previously reported that treatment with tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, prevented neuropathology and associated behavioral deficits in the 3-nitropropionic acid rat model of HD. We therefore examined whether TUDCA would also be neuroprotective in a genetic mouse model of HD. Our results showed that systemically administered TUDCA led to a significant reduction in striatal neuropathology of the R6/2 transgenic HD mouse. Specifically, R6/2 mice began receiving TUDCA at 6 weeks of age and exhibited reduced striatal atrophy, decreased striatal apoptosis, as well as fewer and smaller size ubiquitinated neuronal intranuclear huntingtin inclusions. Moreover, locomotor and sensorimotor deficits were significantly improved in the TUDCA-treated mice. In conclusion, TUDCA is a nontoxic, endogenously produced hydrophilic bile acid that is neuroprotective in a transgenic mouse model of HD and, therefore, may provide a novel and effective treatment in patients with HD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Bile Acids and Salts / administration & dosage
  • Bile Acids and Salts / therapeutic use
  • Cell Nucleus / pathology
  • Corpus Striatum / cytology
  • Corpus Striatum / drug effects
  • Disease Models, Animal
  • Huntington Disease / drug therapy*
  • Huntington Disease / pathology
  • Huntington Disease / physiopathology
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity / drug effects
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control
  • Neurons / cytology
  • Neurons / drug effects
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / therapeutic use*
  • Taurochenodeoxycholic Acid / administration & dosage
  • Taurochenodeoxycholic Acid / therapeutic use*


  • Bile Acids and Salts
  • Neuroprotective Agents
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine