Cited by 497Parkinson's Disease Mechanisms and TreatmentsMitochondrial Function and PathologyNuclear Receptors and Signaling

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

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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·2003·Journal of Clinical Investigation

DOI 10.1172/jci200318797PMC PMC193668

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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-β-hydroxybutyrate (DβHB) 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, DβHB may be a novel neuroprotective therapy for PD.

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Authors: Tieu, K., Perier, C., Caspersen, C., Teismann, P., Wu, D.-C., Yan, S.-D., Naini, A., Vila, M., Jackson-Lewis, V., Ramasamy, R., & Przedborski, S.
Affiliations: Columbia University (US)
Corresponding author: Przedborski, Serge
ORCID: Tieu, Kim
Naini, Ali
Vila, Miquel
Ramasamy, Ravichandran
Przedborski, Serge
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 2003-09-15
Volume: 112
Issue: 6
Pages: 892-901
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci200318797
PMC: PMC193668
OpenAlex: W4242174061
Cited by: 497
References: 43
Citations by year: 2026: 23 · 2025: 35 · 2024: 24 · 2023: 24 · 2022: 44 · 2021: 30 · 2020: 33 · 2019: 25 · 2018: 34 · 2017: 32 · 2016: 23 · 2015: 15 · 2014: 21 · 2013: 10 · 2012: 10
FWCI: 7.79
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
KU ScholarWorks (The University of Kansas) (submittedVersion, other-oa)
Funders: National Institutes of Health (5r29ns037345-05)
National Institute of Neurological Disorders and Stroke (P50-NS38370, R01 NS 38586, R01 NS 42269, R29 NS37345, P01NS011766, R01NS042269, R01NS038586, P50NS038370, P01 NS11766-27A1)
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
Keywords: D-β-hydroxybutyrate, ketone bodies, Parkinson's disease, mitochondrial respiration, MPTP-induced neurotoxicity, dopaminergic neuron loss, complex II, neuroprotection, motor impairment, ATP production, blood-brain barrier
MeSH terms: Adenosine Triphosphate, Animals, Brain, Dopamine, Electron Transport, Humans, Hydrogen Peroxide, Hydroxybutyrate Dehydrogenase, Male, Mice, Inbred C57BL, Mitochondria, Motor Activity, NAD, NADH, NADPH Oxidoreductases, Neurons, Oxygen, Parkinson Disease, Tyrosine 3-Monooxygenase, Dopamine Agents, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Oxidants, Neuroprotective Agents, Cell Respiration, 3-Hydroxybutyric Acid, Electron Transport Complex I, Mice

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

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