The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Dityrosine Cross-linking Promotes Formation of Stable α-Synuclein Polymers
Open accessAbstract
Intracellular proteinaceous aggregates are hallmarks of many common neurodegenerative disorders, and recent studies have shown that alpha-synuclein is a major component of several pathological intracellular inclusions, including Lewy bodies in Parkinson's disease (PD) and glial cell inclusions in multiple system atrophy. However, the molecular mechanisms underlying alpha-synuclein aggregation into filamentous inclusions remain unknown. Since oxidative and nitrative stresses are potential pathogenic mediators of PD and other neurodegenerative diseases, we asked if oxidative and/or nitrative events alter alpha-synuclein and induce it to aggregate. Here we show that exposure of human recombinant alpha-synuclein to nitrating agents (peroxynitrite/CO(2) or myeloperoxidase/H(2)O(2)/nitrite) induces formation of nitrated alpha-synuclein oligomers that are highly stabilized due to covalent cross-linking via the oxidation of tyrosine to form o,o'-dityrosine. We also demonstrate that oxidation and nitration of pre-assembled alpha-synuclein filaments stabilize these filaments to withstand denaturing conditions and enhance formation of SDS-insoluble, heat-stable high molecular mass aggregates. Thus, these data suggest that oxidative and nitrative stresses are involved in mechanisms underlying the pathogenesis of Lewy bodies and glial cell inclusions in PD and multiple system atrophy, respectively, as well as alpha-synuclein pathologies in other synucleinopathies.
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Self-citationMutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
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Factors Determining the Selectivity of Protein Tyrosine Nitration
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Cited by
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
-Synuclein in Parkinson's Disease
Stefanis, L. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a009399 · Cited by 1,446
Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling.
Lee, J., Giordano, S., & Zhang, J. (2012) · Biochemical Journal · doi:10.1042/bj20111451 · Cited by 1,438
Beal, M. F. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00780-3 · Cited by 763
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Metadata
- Authors
- Souza, J. M., Giasson, B. I., Chen, Q., Lee, V. M.-Y., & Ischiropoulos, H.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 275
- Issue
- 24
- Pages
- 18344-18349
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2107434243
- Cited by
- 563
- References
- 10
- FWCI
- 20.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
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