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Open AccessArticle

Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates

1
Institut du Cerveau et de la Moelle épinière (ICM), Inserm U 1127, CNRS UMR 7225, Sorbonne Université, F-75013 Paris, France
2
Instituto de Patología Experimental, CONICET/Universidad Nacional de Salta (UNSa), Salta A4408FVY, Argentina
3
Laboratoire Croissance, Régénération, Réparation et Régénération Tissulaires (CRRET)/ EAC CNRS 7149, Université Paris Est Créteil, Université Paris Est, 94010 Créteil, France
4
Instituto de Medicina Molecular y Celular Aplicada (IMMCA) CONICET/UNT and SIPROSA, Tucumán T4000ILI, Argentina
5
Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo 04023-062, Brazil
*
Author to whom correspondence should be addressed.
Cells 2019, 8(8), 776; https://doi.org/10.3390/cells8080776
Received: 12 June 2019 / Revised: 12 July 2019 / Accepted: 18 July 2019 / Published: 25 July 2019
(This article belongs to the Special Issue Microglia in Neurodegenerative Diseases)
Aggregated forms of the synaptic protein α-synuclein (αS) have been proposed to operate as a molecular trigger for microglial inflammatory processes and neurodegeneration in Parkinson´s disease. Here, we used brain microglial cell cultures activated by fibrillary forms of recombinant human αS to assess the anti-inflammatory and neuroprotective activities of the antibiotic rifampicin (Rif) and its autoxidation product rifampicin quinone (RifQ). Pretreatments with Rif and RifQ reduced the secretion of prototypical inflammatory cytokines (TNF-α, IL-6) and the burst of oxidative stress in microglial cells activated with αS fibrillary aggregates. Note, however, that RifQ was constantly more efficacious than its parent compound in reducing microglial activation. We also established that the suppressive effects of Rif and RifQ on cytokine release was probably due to inhibition of both PI3K- and non-PI3K-dependent signaling events. The control of oxidative stress appeared, however, essentially dependent on PI3K inhibition. Of interest, we also showed that RifQ was more efficient than Rif in protecting neuronal cells from toxic factors secreted by microglia activated by αS fibrils. Overall, data with RifQ are promising enough to justify further studies to confirm the potential of this compound as an anti-parkinsionian drug. View Full-Text
Keywords: aggregation; α-synuclein; microglia; neuroinflammation; Parkinson’s disease; cytokines; neuronal survival aggregation; α-synuclein; microglia; neuroinflammation; Parkinson’s disease; cytokines; neuronal survival
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Acuña, L.; Hamadat, S.; Corbalán, N.S.; González-Lizárraga, F.; dos-Santos-Pereira, M.; Rocca, J.; Sepúlveda Díaz, J.; Del-Bel, E.; Papy-García, D.; Chehín, R.N.; Michel, P.P.; Raisman-Vozari, R. Rifampicin and Its Derivative Rifampicin Quinone Reduce Microglial Inflammatory Responses and Neurodegeneration Induced In Vitro by α-Synuclein Fibrillary Aggregates. Cells 2019, 8, 776.

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