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- Title
D-beta-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease.
- Authors
Tieu, Kim; Perier, Celine; Caspersen, Casper; Teismann, Peter; Wu, Du-Chu; Yan, Shi-Du; Naini, Ali; Vila, Miquel; Jackson-Lewis, Vernice; Ramasamy, Ravichandran; Przedborski, Serge
- 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-beta-hydroxybutyrate (DbetaHB) 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.
- Publication
The Journal of clinical investigation, 2003, Vol 112, Issue 6, p892
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI18797