Abstract
| 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
L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease. / Tieu, Kim; Perier, Celine; Vila, Miquel; Caspersen, Casper; Zhang, Hui-Ping; Teismann, Peter; Jackson-Lewis, Vernice; Stern, David M; Yan, Shi Du; Przedborski, Serge.
In: Annals of Neurology, Vol. 56, No. 1, 07.2004, p. 51-60.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease
AU - Tieu, Kim
AU - Perier, Celine
AU - Vila, Miquel
AU - Caspersen, Casper
AU - Zhang, Hui-Ping
AU - Teismann, Peter
AU - Jackson-Lewis, Vernice
AU - Stern, David M
AU - Yan, Shi Du
AU - Przedborski, Serge
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model
KW - amyloid-beta-peptide
KW - binding alochol-dehydrogenase
KW - coenzyme-A dehydrogenase
KW - mitochondrial complex-I
KW - 3-hydroxyacyl-COA dehydrogenase
KW - dopaminergic neurodegeneration
KW - substantia-nigra
KW - bovine liver
KW - MPTP
U2 - 10.1002/ana.20133
DO - 10.1002/ana.20133
M3 - Article
C2 - 15236401
VL - 56
SP - 51
EP - 60
JO - Annals of Neurology
JF - Annals of Neurology
SN - 0364-5134
IS - 1
ER -