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Cited by 710

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 access
Narhi, Linda, Wood, Stephen J., Steavenson, Shirley, Jiang, Yijia, Wu, Gay May, Anafi, Dan, Kaufman, Stephen A., Martin, Francis, Sitney, Karen, Denis, Paul, Louis, Jean-Claude, Wypych, Jette, Biere, Anja Leona, Citron, Martin·1999·Journal of Biological Chemistry

Abstract

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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CoChat. (2026). Citation check: Both Familial Parkinson's Disease Mutations Accelerate α-Synuclein Aggregation. https://app.cochat.ai/papers/10.1074/jbc.274.14.9843
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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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