Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease - PubMed

Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease

O A Andreassen et al. Ann Neurol. 2001 Jul.

Abstract

Dichloroacetate (DCA) stimulates pyruvate dehydrogenase complex (PDHC) activity and lowers cerebral lactate concentrations. In the R6/2 and N171-82Q transgenic mouse models of Huntington's disease (HD), DCA significantly increased survival, improved motor function, delayed loss of body weight, attenuated the development of striatal neuron atrophy, and prevented diabetes. The percentage of PDHC in the active form was significantly reduced in R6/2 mice at 12 weeks of age, and DCA ameliorated the deficit. These results provide further evidence for a role of energy dysfunction in HD pathogenesis and suggest that DCA may exert therapeutic benefits in HD.

Similar articles

• Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease.

  Ferrante RJ, Andreassen OA, Dedeoglu A, Ferrante KL, Jenkins BG, Hersch SM, Beal MF. Ferrante RJ, et al. J Neurosci. 2002 Mar 1;22(5):1592-9. doi: 10.1523/JNEUROSCI.22-05-01592.2002. J Neurosci. 2002. PMID: 11880489 Free PMC article.

• Altered selenium status in Huntington's disease: neuroprotection by selenite in the N171-82Q mouse model.

  Lu Z, Marks E, Chen J, Moline J, Barrows L, Raisbeck M, Volitakis I, Cherny RA, Chopra V, Bush AI, Hersch S, Fox JH. Lu Z, et al. Neurobiol Dis. 2014 Nov;71:34-42. doi: 10.1016/j.nbd.2014.06.022. Epub 2014 Jul 8. Neurobiol Dis. 2014. PMID: 25014023

• Lipoic acid improves survival in transgenic mouse models of Huntington's disease.

  Andreassen OA, Ferrante RJ, Dedeoglu A, Beal MF. Andreassen OA, et al. Neuroreport. 2001 Oct 29;12(15):3371-3. doi: 10.1097/00001756-200110290-00044. Neuroreport. 2001. PMID: 11711888

• The use of the R6 transgenic mouse models of Huntington's disease in attempts to develop novel therapeutic strategies.

  Li JY, Popovic N, Brundin P. Li JY, et al. NeuroRx. 2005 Jul;2(3):447-64. doi: 10.1602/neurorx.2.3.447. NeuroRx. 2005. PMID: 16389308 Free PMC article. Review.

• Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications.

  Tataranni T, Piccoli C. Tataranni T, et al. Oxid Med Cell Longev. 2019 Nov 14;2019:8201079. doi: 10.1155/2019/8201079. eCollection 2019. Oxid Med Cell Longev. 2019. PMID: 31827705 Free PMC article. Review.

Cited by

• Integrated multi-omics analysis of Huntington disease identifies pathways that modulate protein aggregation.

  Pradhan SS, Thota SM, Rajaratnam S, Bhagavatham SKS, Pulukool SK, Rathnakumar S, Phalguna KS, Dandamudi RB, Pargaonkar A, Joseph P, Joshy EV, Sivaramakrishnan V. Pradhan SS, et al. Dis Model Mech. 2022 Oct 1;15(10):dmm049492. doi: 10.1242/dmm.049492. Epub 2022 Oct 31. Dis Model Mech. 2022. PMID: 36052548 Free PMC article.

• Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

  Naseri NN, Xu H, Bonica J, Vonsattel JP, Cortes EP, Park LC, Arjomand J, Gibson GE. Naseri NN, et al. J Neuropathol Exp Neurol. 2015 Jun;74(6):527-37. doi: 10.1097/NEN.0000000000000197. J Neuropathol Exp Neurol. 2015. PMID: 25978848 Free PMC article.

• Therapeutic effects of cystamine in a murine model of Huntington's disease.

  Dedeoglu A, Kubilus JK, Jeitner TM, Matson SA, Bogdanov M, Kowall NW, Matson WR, Cooper AJ, Ratan RR, Beal MF, Hersch SM, Ferrante RJ. Dedeoglu A, et al. J Neurosci. 2002 Oct 15;22(20):8942-50. doi: 10.1523/JNEUROSCI.22-20-08942.2002. J Neurosci. 2002. PMID: 12388601 Free PMC article.

• Translating therapies for Huntington's disease from genetic animal models to clinical trials.

  Hersch SM, Ferrante RJ. Hersch SM, et al. NeuroRx. 2004 Jul;1(3):298-306. doi: 10.1602/neurorx.1.3.298. NeuroRx. 2004. PMID: 15717031 Free PMC article. Review.

• A mitochondrial basis for Huntington's disease: therapeutic prospects.

  Chakraborty J, Rajamma U, Mohanakumar KP. Chakraborty J, et al. Mol Cell Biochem. 2014 Apr;389(1-2):277-91. doi: 10.1007/s11010-013-1951-9. Epub 2013 Dec 29. Mol Cell Biochem. 2014. PMID: 24374792 Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Other Literature Sources

  • The Lens - Patent Citations Database

• Medical

  • MedlinePlus Health Information