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Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease
Open accessAbstract
Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3 immunohistochemistry on the postmortem human brain, we observed a positive correlation between the degree of neuronal loss in dopaminergic (DA) cell groups affected in the mesencephalon of PD patients and the percentage of caspase-3-positive neurons in these cell groups in control subjects and a significant decrease of caspase-3-positive pigmented neurons in the substantia nigra pars compacta of PD patients compared with controls that also could be observed in an animal model of PD. This suggests that neurons expressing caspase-3 are more sensitive to the pathological process than those that do not express the protein. In addition, using an antibody raised against activated caspase-3, the percentage of active caspase-3-positive neurons among DA neurons was significantly higher in PD patients than in controls. Finally, electron microscopy analysis in the human brain and in vitro data suggest that caspase-3 activation precedes and is not a consequence of apoptotic cell death in PD.
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Cites
Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease
Hirsch, E., Graybiel, A. M., & Agid, Y. A. (1988) · Nature · doi:10.1038/334345a0 · Cited by 1,301
Self-citationDistinct mechanisms underlie neurotoxin-mediated cell death in cultured dopaminergic neurons
Lotharius, J., Dugan, L. L., & O’Malley, K. L. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-04-01284.1999 · Cited by 403
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
Autophagy and apoptosis dysfunction in neurodegenerative disorders
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christoffersson, J., Chaabane, W., Moghadam, A. R., Kashani, H. H., et al. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.004 · Cited by 1,039
Mitochondrial dysfunction and oxidative stress in Parkinson's disease
Subramaniam, S. R., & Chesselet, M.-F. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.04.004 · Cited by 913
Mitochondrial dysfunction in Parkinson's disease
Winklhofer, K. F., & Haass, C. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.08.013 · Cited by 688
Metadata
- Authors
- Hartmann, A., Hunot, S., Michel, P. P., Muriel, M.-P., Vyas, S., Faucheux, B. A., Mouatt-Prigent, A., Turmel, H., Srinivasan, A., Ruberg, M., Evan, G. I., Agid, Y., & Hirsch, E. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-25
- Volume
- 97
- Issue
- 6
- Pages
- 2875-2880
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2096298540
- Cited by
- 715
- References
- 2
- FWCI
- 33.72
- Type
- journal article
- Language
- en
- Open access
- green
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- Hartmann, A., Hunot, S., Michel, P. P., Muriel, M.-P., Vyas, S., Faucheux, B. A., Mouatt-Prigent, A., Turmel, H., Srinivasan, A., Ruberg, M., Evan, G. I., Agid, Y., & Hirsch, E. C. (2000). Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.040556597
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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