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Cited by 684

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The Herbicide Paraquat Causes Up-regulation and Aggregation of α-Synuclein in Mice

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Manning-Bog, Amy B., McCormack, Alison L., Li, Jie, Uversky, Vladimir N., Fink, Anthony L., Di Monte, Donato A.·2002·Journal of Biological Chemistry

Abstract

alpha-Synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including Parkinson's disease (PD). However, mechanisms that promote intraneuronal alpha-synuclein assembly remain poorly understood. Because pesticides, particularly the herbicide paraquat, have been suggested to play a role as PD risk factors, the hypothesis that interactions between alpha-synuclein and these environmental agents may contribute to aggregate formation was tested in this study. Paraquat markedly accelerated the in vitro rate of alpha-synuclein fibril formation in a dose-dependent fashion. When mice were exposed to the herbicide, brain levels of alpha-synuclein were significantly increased. This up-regulation followed a consistent pattern, with higher alpha-synuclein at 2 days after each of three weekly paraquat injections and with protein levels returning to control values by day 7 post-treatment. Paraquat exposure was also accompanied by aggregate formation. Thioflavine S-positive structures accumulated within neurons of the substantia nigra pars compacta, and dual labeling and confocal imaging confirmed that these aggregates contained alpha-synuclein. The results suggest that up-regulation of alpha-synuclein as a consequence of toxicant insult and direct interactions between the protein and environmental agents are potential mechanisms leading to alpha-synuclein pathology in neurodegenerative disorders.

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Metadata

Authors
Manning-Bog, A. B., McCormack, A. L., Li, J., Uversky, V. N., Fink, A. L., & Di Monte, D. A.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2002-01
Volume
277
Issue
3
Pages
1641-1644
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1591724033
Cited by
684
References
5
FWCI
26.37
Type
journal article
Language
en
Open access
hybrid

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CoChat. (2026). Citation check: The Herbicide Paraquat Causes Up-regulation and Aggregation of α-Synuclein in Mice. https://app.cochat.ai/papers/10.1074/jbc.c100560200
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Manning-Bog, A. B., McCormack, A. L., Li, J., Uversky, V. N., Fink, A. L., & Di Monte, D. A. (2002). The Herbicide Paraquat Causes Up-regulation and Aggregation of α-Synuclein in Mice. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.c100560200

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.