The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Both Familial Parkinson's Disease Mutations Accelerate α-Synuclein Aggregation
Open accessAbstract
Parkinson's disease (PD) is a neurodegenerative disorder that is pathologically characterized by the presence of intracytoplasmic Lewy bodies, the major component of which are filaments consisting of alpha-synuclein. Two recently identified point mutations in alpha-synuclein are the only known genetic causes of PD, but their pathogenic mechanism is not understood. Here we show that both wild type and mutant alpha-synuclein form insoluble fibrillar aggregates with antiparallel beta-sheet structure upon incubation at physiological temperature in vitro. Importantly, aggregate formation is accelerated by both PD-linked mutations. Under the experimental conditions, the lag time for the formation of precipitable aggregates is about 280 h for the wild type protein, 180 h for the A30P mutant, and only 100 h for the A53T mutant protein. These data suggest that the formation of alpha-synuclein aggregates could be a critical step in PD pathogenesis, which is accelerated by the PD-linked mutations.
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Metadata
- Authors
- Narhi, L., Wood, S. J., Steavenson, S., Jiang, Y., Wu, G. M., Anafi, D., Kaufman, S. A., Martin, F., Sitney, K., Denis, P., Louis, J.-C., Wypych, J., Biere, A. L., & Citron, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-04
- Volume
- 274
- Issue
- 14
- Pages
- 9843-9846
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2116597539
- Cited by
- 710
- References
- 16
- FWCI
- 33.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Narhi, L., Wood, S. J., Steavenson, S., Jiang, Y., Wu, G. M., Anafi, D., Kaufman, S. A., Martin, F., Sitney, K., Denis, P., Louis, J.-C., Wypych, J., Biere, A. L., & Citron, M. (1999). Both Familial Parkinson's Disease Mutations Accelerate α-Synuclein Aggregation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.14.9843
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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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