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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride Neurotoxicity Is Attenuated in Mice Overexpressing Bcl-2
Open accessAbstract
The proto-oncogene Bcl-2 rescues cells from a wide variety of insults. Recent evidence suggests that Bcl-2 protects against free radicals and that it increases mitochondrial calcium-buffering capacity. The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride (MPTP) is thought to involve both mitochondrial dysfunction and free radical generation. We therefore investigated MPTP neurotoxicity in both Bcl-2 overexpressing mice and littermate controls. MPTP-induced depletion of dopamine and loss of [3 H]mazindol binding were significantly attenuated in Bcl-2 overexpressing mice. Protection was more profound with an acute dosing regimen than with daily MPTP administration over 5 d. 1-Methyl-4-phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2 overexpressing mice and littermates. Bcl-2 blocked MPP+-induced activation of caspases. MPTP-induced increases in free 3-nitrotyrosine levels were blocked in Bcl-2 overexpressing mice. These results indicate that Bcl-2 overexpression protects against MPTP neurotoxicity by mechanisms that may involve both antioxidant activity and inhibition of apoptotic pathways.
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Citations
Cited by
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
Blum, D., Torch, S., Lambeng, N., Nissou, M.-F., Benabid, A.-L., Sadoul, R., & Verna, J.-M. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(01)00003-x · Cited by 1,246
Experimental models of Parkinson's disease
Beal, M. F. (2001) · Nature Reviews Neuroscience · doi:10.1038/35072550 · Cited by 637
Self-citationThe BCL2 family: from apoptosis mechanisms to new advances in targeted therapy
Vogler, M., Braun, Y., Smith, V. M., Westhoff, M.-A., Pereira, R. S., Pieper, N. M., Anders, M., Callens, M., Vervliet, T., Abbas, M., et al. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02176-0 · Cited by 462
Vila, M., Jackson-Lewis, V., Vukosavic, S., Djaldetti, R., Liberatore, G., Offen, D., Korsmeyer, S. J., & Przedborski, S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051633998 · Cited by 372
Metadata
- Authors
- Yang, L., Matthews, R. T., Schulz, J. B., Klockgether, T., Liao, A. W., Martinou, J.-C., Penney, J. B., Hyman, B. T., & Beal, M. F.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1998-10-15
- Volume
- 18
- Issue
- 20
- Pages
- 8145-8152
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2101060066
- Cited by
- 199
- References
- 0
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Yang, L., Matthews, R. T., Schulz, J. B., Klockgether, T., Liao, A. W., Martinou, J.-C., Penney, J. B., Hyman, B. T., & Beal, M. F. (1998). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride Neurotoxicity Is Attenuated in Mice Overexpressing Bcl-2. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.18-20-08145.1998
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