Protection by synergistic effects of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial cell line-derived neurotrophic factor gene transfer in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
2000 | journal article; research paper. A publication with affiliation to the University of Göttingen.
Jump to: Cite & Linked | Documents & Media | Details | Version history
Cite this publication
Protection by synergistic effects of adenovirus-mediated X-chromosome-linked inhibitor of apoptosis and glial cell line-derived neurotrophic factor gene transfer in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease
Eberhardt, O.; Coelln, R. V.; Kugler, S. ; Lindenau, J.; Rathke-Hartlieb, S.; Gerhardt, E. & Haid, S. et al. (2000)
The Journal of Neuroscience, 20(24) pp. 9126-9134. DOI: https://doi.org/10.1523/JNEUROSCI.20-24-09126.2000
Documents & Media
Details
- Authors
- Eberhardt, O.; Coelln, Rainer V.; Kugler, S. ; Lindenau, J.; Rathke-Hartlieb, S; Gerhardt, Ellen ; Haid, S.; Isenmann, Stefan; Gravel, C.; Srinivasan, A.; Bähr, Mathias ; Weller, M; Dichgans, J.; Schulz, Joerg B.
- Abstract
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical, and neuropathological changes reminiscent of those occurring in idiopathic Parkinson's disease (PD). Here we show that a peptide caspase inhibitor, N-benzyloxycarbonyl- val-ala-asp-fluoromethyl ketone, or adenoviral gene transfer (AdV) of a protein caspase inhibitor, X-chromosome-linked inhibitor of apoptosis (XIAP), prevent cell death of dopaminergic substantia nigra pars compacta (SNpc) neurons induced by MPTP or its active metabolite 1-methyl-4-phenylpyridinium in vitro and in vivo. Because the MPTP-induced decrease in striatal concentrations of dopamine and its metabolites does not differ between AdV-XIAP- and control vector-treated mice, this protection is not associated with a preservation of nigrostriatal terminals. In contrast, the combination of adenoviral gene transfer of XIAP and of the glial cell line-derived neurotrophic factor to the striatum provides synergistic effects, rescuing dopaminergic SNpc neurons from cell death and maintaining their nigrostriatal terminals. These data suggest that a combination of a caspase inhibitor, which blocks death, and a neurotrophic factor, which promotes the specific function of the rescued neurons, may be a promising strategy for the treatment of PD.
- Issue Date
- 2000
- Journal
- The Journal of Neuroscience
- ISSN
- 0270-6474
- Language
- English