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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein.

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.[1]

References

  1. The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. Manning-Bog, A.B., McCormack, A.L., Li, J., Uversky, V.N., Fink, A.L., Di Monte, D.A. J. Biol. Chem. (2002) [Pubmed]
 
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