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

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

• Book ID: 102705277
• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 642 KB
• Volume: 56
• Category: Article
• ISSN: 0364-5134
• DOI: 10.1002/ana.20133

✦ Synopsis

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.