Version 1
: Received: 4 July 2024 / Approved: 4 July 2024 / Online: 4 July 2024 (11:05:00 CEST)
How to cite:
Quarta, S.; Sandre, M.; Ruvoletto, M.; Campagnolo, M.; Emmi, A.; Biasiolo, A.; Pontisso, P.; Antonini, A. Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease. Preprints2024, 2024070434. https://doi.org/10.20944/preprints202407.0434.v1
Quarta, S.; Sandre, M.; Ruvoletto, M.; Campagnolo, M.; Emmi, A.; Biasiolo, A.; Pontisso, P.; Antonini, A. Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease. Preprints 2024, 2024070434. https://doi.org/10.20944/preprints202407.0434.v1
Quarta, S.; Sandre, M.; Ruvoletto, M.; Campagnolo, M.; Emmi, A.; Biasiolo, A.; Pontisso, P.; Antonini, A. Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease. Preprints2024, 2024070434. https://doi.org/10.20944/preprints202407.0434.v1
APA Style
Quarta, S., Sandre, M., Ruvoletto, M., Campagnolo, M., Emmi, A., Biasiolo, A., Pontisso, P., & Antonini, A. (2024). Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease. Preprints. https://doi.org/10.20944/preprints202407.0434.v1
Chicago/Turabian Style
Quarta, S., Patrizia Pontisso and Angelo Antonini. 2024 "Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease" Preprints. https://doi.org/10.20944/preprints202407.0434.v1
Abstract
In Parkinson's disease, neuroinflammation is a complex defense mechanism. Activated microglia and Proteinase-activated receptor-2 (PAR2) are key points in the regulation of neuroinflammation. 1-Piperidin Propionic Acid (1-PPA) has been recently described as a novel inhibitor of PAR2. The aim of our study was to evaluate the effect of 1-PPA in neuroinflammation and microglial activation in Parkinson's disease. Protein aggregates and PAR2 expression were analyzed by thioflavin S assay and immunofluorescence in cultured human fibroblasts from Parkinson's patients, treated or not with 1-PPA. A significant decrease of amyloid aggregates and expression of PAR2 were observed after 1-PPA treatment in all patients. A parallel decrease of PAR2 expression, that was higher in sporadic Parkinson’s patients, was also observed both at transcriptional and protein level. In addition, in mouse LPS-activated microglia, the inflammatory profile was significantly downregulated after 1-PPA treatment, with a remarkable decrease of IL-1, IL-6 and TNF-togheter with PAR2 decreased expression.In conclusion, 1-PPA determines reduced neuroglia inflammation and amyloid aggregates formation, suggesting that pharmacological inhibition of PAR2 could be proposed as a novel strategy to control neuroinflammation.
Medicine and Pharmacology, Neuroscience and Neurology
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