The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin–proteasome system
Open accessAbstract
Sporadic Parkinson's disease (PD) is most likely caused by a combination of environmental exposures and genetic susceptibilities, although there are rare monogenic forms of the disease. Mitochondrial impairment at complex I, oxidative stress, alpha-synuclein aggregation, and dysfunctional protein degradation, have been implicated in PD pathogenesis, but how they are related to each other is unclear. To further evaluated PD pathogenesis here, we used in vivo and in vitro models of chronic low-grade complex I inhibition with the pesticide rotenone. Chronic rotenone exposure in vivo caused oxidative modification of DJ-1, accumulation of alpha-synuclein, and proteasomal impairment. Interestingly, the effects become more regionally restricted such that systemic complex I inhibition eventually results in highly selective degeneration of the nigrostriatal pathway. DJ-1 modifications, alpha-synuclein accumulation, and proteasomal dysfunction were also seen in vitro and these effects could be prevented with alpha-tocopherol. Thus, chronic exposure to a pesticide and mitochondrial toxin brings into play three systems, DJ-1, alpha-synuclein, and the ubiquitin-proteasome system, and implies that mitochondrial dysfunction and oxidative stress link environmental and genetic forms of the disease.
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Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1
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Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase
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Are ubiquitination pathways central to Parkinson’s disease?
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Cited by
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Mitochondria in the aetiology and pathogenesis of Parkinson's disease
Schapira, A. H. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70327-7 · Cited by 883
α-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson’s disease
Di Maio, R., Barrett, P. J., Hoffman, E. K., Barrett, C. W., Zharikov, A., Borah, A., Hu, X., McCoy, J., Chu, C. T., Burton, E. A., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf3634 · Cited by 619
Self-citationPathological roles of α-synuclein in neurological disorders
Vekrellis, K., Xilouri, M., Emmanouilidou, E., Rideout, H. J., & Stefanis, L. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(11)70213-7 · Cited by 357
Yadava, N., & Nicholls, D. G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.0212-07.2007 · Cited by 272
Metadata
- Authors
- Betarbet, R., Canet-Aviles, R. M., Sherer, T. B., Mastroberardino, P. G., McLendon, C., Kim, J.-H., Lund, S., Na, H.-M., Taylor, G., Bence, N. F., Kopito, R., Seo, B. B., Yagi, T., Yagi, A., Klinefelter, G., Cookson, M. R., & Greenamyre, J. T.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 22
- Issue
- 2
- Pages
- 404-420
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2041831342
- Cited by
- 342
- References
- 8
- FWCI
- 18.61
- Type
- journal article
- Language
- en
- Open access
- green
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- Betarbet, R., Canet-Aviles, R. M., Sherer, T. B., Mastroberardino, P. G., McLendon, C., Kim, J.-H., Lund, S., Na, H.-M., Taylor, G., Bence, N. F., Kopito, R., Seo, B. B., Yagi, T., Yagi, A., Klinefelter, G., Cookson, M. R., & Greenamyre, J. T. (2006). Intersecting pathways to neurodegeneration in Parkinson's disease: Effects of the pesticide rotenone on DJ-1, α-synuclein, and the ubiquitin–proteasome system. Neurobiology of Disease. https://doi.org/10.1016/j.nbd.2005.12.003
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