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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2007

Open Access 01-12-2007 | Research

Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated α-synuclein

Authors: Jinghua Jin, Feng-Shiun Shie, Jun Liu, Yan Wang, Jeanne Davis, Aimee M Schantz, Kathleen S Montine, Thomas J Montine, Jing Zhang

Published in: Journal of Neuroinflammation | Issue 1/2007

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Abstract

Background

The pathogenesis of idiopathic Parkinson's disease (PD) remains elusive, although evidence has suggested that neuroinflammation characterized by activation of resident microglia in the brain may contribute significantly to neurodegeneration in PD. It has been demonstrated that aggregated α-synuclein potently activates microglia and causes neurotoxicity. However, the mechanisms by which aggregated α-synuclein activates microglia are not understood fully.

Methods

We investigated the role of prostaglandin E2 receptor subtype 2 (EP2) in α-synuclein aggregation-induced microglial activation using ex vivo, in vivo and in vitro experimental systems.

Results

Results demonstrated that ablation of EP2(EP2-/-) significantly enhanced microglia-mediated ex vivo clearance of α-synuclein aggregates (from mesocortex of Lewy body disease patients) while significantly attenuating neurotoxicity and extent of α-synuclein aggregation in mice treated with a parkinsonian toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Furthermore, we report that reduced neurotoxicity by EP2-/- microglia could be attributed to suppressed translocation of a critical cytoplasmic subunit (p47-phox) of NADPH oxidase (PHOX) to the membranous compartment after exposure to aggregated α-synuclein.

Conclusion

Thus, it appears that microglial EP2 plays a critical role in α-synuclein-mediated neurotoxicity.
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Metadata
Title
Prostaglandin E2 receptor subtype 2 (EP2) regulates microglial activation and associated neurotoxicity induced by aggregated α-synuclein
Authors
Jinghua Jin
Feng-Shiun Shie
Jun Liu
Yan Wang
Jeanne Davis
Aimee M Schantz
Kathleen S Montine
Thomas J Montine
Jing Zhang
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2007
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/1742-2094-4-2

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