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 language | English |
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Pages (from-to) | 51-60 |
Number of pages | 10 |
Journal | Annals of Neurology |
Volume | 56 |
Issue number | 1 |
Early online date | 28 Jun 2004 |
DOIs | |
Publication status | Published - 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