L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease

Kim Tieu, Celine Perier, Miquel Vila, Casper Caspersen, Hui-Ping Zhang, Peter Teismann, Vernice Jackson-Lewis, David M Stern, Shi Du Yan, Serge Przedborski

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36 Citations (Scopus)

Abstract

The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impairs mitochondrial respiration and damages dopaminergic neurons as seen in Parkinson's disease (PD). Here, we report that L-3-hydroxyacyl-CoA dehydrogenase type II/amyloid binding alcohol dehydrogenase (HADH II/ABAD), a mitochondrial oxidoreductase enzyme involved in neuronal survival, is downregulated in PD patients and in MPTP-intoxicated mice. We also show that transgenic mice with increased expression of human HADH II/ABAD are significantly more resistant to MPTP than their wild-type littermates. This effect appears to be mediated by overexpression of HADH II/ABAD mitigating MPTP-induced impairment of oxidative phosphorylation and ATP production. This study demonstrates that HADH II/ABAD modulates MPTP neurotoxicity and suggests that HADH II/ABAD mimetics may provide protective benefit in the treatment of PD.
Original languageEnglish
Pages (from-to)51-60
Number of pages10
JournalAnnals of Neurology
Volume56
Issue number1
Early online date28 Jun 2004
DOIs
Publication statusPublished - Jul 2004

Keywords

  • 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model
  • amyloid-beta-peptide
  • binding alochol-dehydrogenase
  • coenzyme-A dehydrogenase
  • mitochondrial complex-I
  • 3-hydroxyacyl-COA dehydrogenase
  • dopaminergic neurodegeneration
  • substantia-nigra
  • bovine liver
  • MPTP

Cite this

Tieu, K., Perier, C., Vila, M., Caspersen, C., Zhang, H-P., Teismann, P., Jackson-Lewis, V., Stern, D. M., Yan, S. D., & Przedborski, S. (2004). L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease. Annals of Neurology, 56(1), 51-60. https://doi.org/10.1002/ana.20133