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 |
|---|---|
| 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
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