D ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease

K. Tieu, C. Perier, C. Caspersen, Peter Teismann, D. C. Wu, S. D. Yan, A. Naini, M. Vila, V. Jackson-Lewis, R. Ramasamy, S. Przedborski

Research output: Contribution to journalArticle

251 Citations (Scopus)

Abstract

Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body D-p-hydroxybutyrate (DPHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.

Original languageEnglish
Pages (from-to)892-901
Number of pages9
JournalThe Journal of Clinical Investigation
Volume112
Issue number6
DOIs
Publication statusPublished - 15 Sep 2003

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model
  • electron-transport chain
  • complex-I
  • dopaminergic neurotoxicity
  • dietary restriction
  • nitric-oxide
  • rat-liver
  • brain
  • MPTP
  • neurodegeneration

Cite this

Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D. C., Yan, S. D., ... Przedborski, S. (2003). D ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. The Journal of Clinical Investigation, 112(6), 892-901. https://doi.org/10.1172/JCI200318797

D ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. / Tieu, K.; Perier, C.; Caspersen, C.; Teismann, Peter; Wu, D. C.; Yan, S. D.; Naini, A.; Vila, M.; Jackson-Lewis, V.; Ramasamy, R.; Przedborski, S.

In: The Journal of Clinical Investigation, Vol. 112, No. 6, 15.09.2003, p. 892-901.

Research output: Contribution to journalArticle

Tieu, K, Perier, C, Caspersen, C, Teismann, P, Wu, DC, Yan, SD, Naini, A, Vila, M, Jackson-Lewis, V, Ramasamy, R & Przedborski, S 2003, 'D ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease', The Journal of Clinical Investigation, vol. 112, no. 6, pp. 892-901. https://doi.org/10.1172/JCI200318797
Tieu, K. ; Perier, C. ; Caspersen, C. ; Teismann, Peter ; Wu, D. C. ; Yan, S. D. ; Naini, A. ; Vila, M. ; Jackson-Lewis, V. ; Ramasamy, R. ; Przedborski, S. / D ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. In: The Journal of Clinical Investigation. 2003 ; Vol. 112, No. 6. pp. 892-901.
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AB - Parkinson disease (PD) is a neurodegenerative disorder characterized by a loss of the nigrostriatal dopaminergic neurons accompanied by a deficit in mitochondrial respiration. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that causes dopaminergic neurodegeneration and a mitochondrial deficit reminiscent of PD. Here we show that the infusion of the ketone body D-p-hydroxybutyrate (DPHB) in mice confers partial protection against dopaminergic neurodegeneration and motor deficits induced by MPTP. These effects appear to be mediated by a complex II-dependent mechanism that leads to improved mitochondrial respiration and ATP production. Because of the safety record of ketone bodies in the treatment of epilepsy and their ability to penetrate the blood-brain barrier, DbetaHB may be a novel neuroprotective therapy for PD.

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