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

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 +3 more·2003·Journal of Clinical Investigation

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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  • β-hydroxybutyrate protects dopaminergic neurons in an animal model of PD.

    “also protects dopaminergic neurons in an animal model of PD”

    From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Tieu et al., 2003

  • Carnitine and β-hydroxybutyrate has shown to protect against MPTP toxicity.

    “Carnitine and β-hydroxybutyrate has shown to protect against MPTP toxicity189-191.”

    From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [191]

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Research works printed but not linked: 2

  1. [2]Fahn, S., and Przedborski, S. 2000. Parkinsonism. In Merritt's neurology. L.P. Rowland, editor. Lippincott Williams & Wilkins. New York, New York, USA. 679-693.
  2. [41]Mandir, A.S., et al. 1999. Poly (ADP-ribose) polymerase activation mediates MPTP-induced parkinsonism. Proc. Natl. Acad. Sci. U. S. A. 96 :5774-5779.

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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
Venue
Journal of Clinical Investigation
Published
2003-09-15
Volume
112
Issue
6
Pages
892-901
ISSN
0021-9738 (ISSN-L)
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
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 › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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