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

ACUÑA, NULL; HAMADAT, NULL; CORBALÁN, NULL; GONZÁLEZ-LIZÁRRAGA, NULL; DOS-SANTOS-PEREIRA, NULL; ROCCA, NULL; DÍAZ, NULL; DEL-BEL, NULL; PAPY-GARCÍA, NULL; CHEHÍN, NULL; MICHEL, NULL; RAISMAN-VOZARI, NULL

Cells

MDPI

Lugar: Lucerna; Año: 2019 vol. 8

Aggregated forms of the synaptic protein ↵-synuclein (↵S) 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 ↵S 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-↵, IL-6) and the burst of oxidative stress in microglial cells activated with ↵S fibrillary aggregates. Note, however, that RifQ was constantly more ecacious than its parent compound in reducing microglial activation. We also established that the suppressive e↵ects 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 ecient than Rif in protecting neuronal cells from toxic factors secreted by microglia activated by ↵S fibrils. Overall, data with RifQ are promising enough to justify further studies to confirm the potential of this compound as an anti-parkinsionian drug