The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism
Abstract
Drugs currently used for patients with Parkinson's disease provide temporary relief of symptoms but do not halt or slow the underlying neurodegenerative disease process. Increasing evidence suggests that neurons die in Parkinson's disease by a process called apoptosis, which may be triggered by mitochondrial impairment and oxidative stress. We report that two novel synthetic inhibitors of the tumor suppressor protein p53, pifithrin‐α (PFT‐α) and Z‐1‐117, are highly effective in protecting midbrain dopaminergic neurons and improving behavioral outcome in a mouse model of Parkinson's disease. Mice given intraperitoneal injections of PFT‐α or Z‐1‐117 exhibited improved motor function, reduced damage to nigrostriatal dopaminergic neurons and reduced depletion of dopamine and its metabolites after exposure to the toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP). MPTP caused an increase in the level of the proapoptotic protein Bax, which was prevented by giving mice PFT‐α and Z‐1‐117. PFT‐α and Z‐1‐117 also suppressed Bax production and apoptosis in cultured dopaminergic cells exposed to MPP+. Our findings demonstrate a pivotal role for p53 in experimental parkinsonism and identify a novel class of synthetic p53 inhibitors with clinical potential.
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Cites
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Apoptosis in neurodegenerative disorders
Mattson, M. P. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35040009 · Cited by 1,605
Self-citationA Chemical Inhibitor of p53 That Protects Mice from the Side Effects of Cancer Therapy
Komarov, P. G., Komarova, E. A., Kondratov, R. V., Christov-Tselkov, K., Coon, J. S., Chernov, M. V., & Gudkov, A. V. (1999) · Science · doi:10.1126/science.285.5434.1733 · Cited by 1,270
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Ladenheim, B., Krasnova, I. N., Deng, X., Oyler, J. M., Polettini, A., Moran, T. H., Huestis, M. A., & Cadet, J. L. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.6.1247 · Cited by 131
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Cited by
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
Blinded by the Light: The Growing Complexity of p53
Vousden, K. H., & Prives, C. (2009) · Cell · doi:10.1016/j.cell.2009.04.037 · Cited by 3,163
Ageing and neuronal vulnerability
Mattson, M. P., & Magnus, T. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1886 · Cited by 957
Self-citationApoptosis and Oxidative Stress in Neurodegenerative Diseases
Radi, E., Formichi, P., Battisti, C., & Federico, A. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-132738 · Cited by 630
Li, Y., Perry, T., Kindy, M. S., Harvey, B. K., Tweedie, D., Holloway, H. W., Powers, K., Shen, H., Egan, J. M., Sambamurti, K., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806720106 · Cited by 589
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Metadata
- Authors
- Duan, W., Zhu, X., Ladenheim, B., Yu, Q., Guo, Z., Oyler, J., Cutler, R. G., Cadet, J. L., Greig, N. H., & Mattson, M. P.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2002-09-24
- Volume
- 52
- Issue
- 5
- Pages
- 597-606
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2022762621
- Cited by
- 204
- References
- 6
- FWCI
- 9.42
- Type
- journal article
- Language
- en
- Open access
- closed
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- Duan, W., Zhu, X., Ladenheim, B., Yu, Q., Guo, Z., Oyler, J., Cutler, R. G., Cadet, J. L., Greig, N. H., & Mattson, M. P. (2002). p53 inhibitors preserve dopamine neurons and motor function in experimental parkinsonism. Annals of Neurology. https://doi.org/10.1002/ana.10350
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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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