The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Inducible expression of mutant alpha-synuclein decreases proteasome activity and increases sensitivity to mitochondria-dependent apoptosis
Abstract
Parkinson's disease (PD) is a common progressive neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra. Although mutations in alpha-synuclein have been identified in autosomal dominant PD, the mechanism by which dopaminergic neural cell death occurs remains unknown. Proteins encoded by two other genes in which mutations cause familial PD, parkin and UCH-L1, are involved in regulation of the ubiquitin-proteasome pathway, suggesting that dysregulation of the ubiquitin-proteasome pathway is involved in the mechanism by which these mutations cause PD. We established inducible PC12 cell lines in which wild-type or mutant alpha-synuclein can be de-repressed by removing doxycycline. Differentiated PC12 cell lines expressing mutant alpha-synuclein showed decreased activity of proteasomes without direct toxicity. Cells expressing mutant alpha-synuclein showed increased sensitivity to apoptotic cell death when treated with sub-toxic concentrations of an exogenous proteasome inhibitor. Apoptosis was accompanied by mitochondrial depolarization and elevation of caspase-3 and -9, and was blocked by cyclosporin A. These data suggest that expression of mutant alpha-synuclein results in sensitivity to impairment of proteasome activity, leading to mitochondrial abnormalities and neuronal cell death.
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Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease.
Gibb, W. R., & Lees, A. J. (1988) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.51.6.745 · Cited by 3,481
Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
Shimura, H., Hattori, N., Kubo, S.-I., Mizuno, Y., Asakawa, S., Minoshima, S., Shimizu, N., Iwai, K., Chiba, T., Tanaka, K., et al. (2000) · Nature Genetics · doi:10.1038/77060 · Cited by 2,024 · cited 1×
“Proteins encloded by other causal genes of familial PD, parkin and UCH-L1, are a ubiquitin-protein ligase and a deubiquitinating enzyme, respectively (16,19).”
BackgroundAnkarcrona, M., Dypbukt, J. M., Bonfoco, E., Zhivotovsky, B., Orrenius, S., Lipton, S. A., & Nicotera, P. (1995) · Neuron · doi:10.1016/0896-6273(95)90186-8 · Cited by 1,884
Zhang, Y., Gao, J., Chung, K. K. K., Huang, H., Dawson, V. L., & Dawson, T. M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.240347797 · Cited by 982
Proteasomal function is impaired in substantia nigra in Parkinson’s disease
McNaught, K. S. P., & Jenner, P. (2001) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01701-8 · Cited by 653
Cited by
Dauer, W., & Przedborski, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00568-3 · Cited by 5,469
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Zhang, W., Wang, T., Pei, Z., Miller, D. S., Wu, X., Block, M. L., Wilson, B., Zhang, W., Zhou, Y., Hong, J.-S., et al. (2005) · The FASEB Journal · doi:10.1096/fj.04-2751com · Cited by 1,265
Mitochondria in neuroplasticity and neurological disorders
Mattson, M. P., Gleichmann, M., & Cheng, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.010 · Cited by 1,081
Ageing and neuronal vulnerability
Mattson, M. P., & Magnus, T. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1886 · Cited by 957
Metadata
- Authors
- Tanaka, Y.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-04-01
- Volume
- 10
- Issue
- 9
- Pages
- 919-926
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2104912043
- Cited by
- 497
- References
- 8
- FWCI
- 25.65
- Type
- journal article
- Language
- en
- Open access
- closed
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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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