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

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

Cells (2019-07-28)
Leonardo Acuña, Sabah Hamadat, Natalia S Corbalán, Florencia González-Lizárraga, Mauricio Dos-Santos-Pereira, Jérémy Rocca, Julia Sepúlveda Díaz, Elaine Del-Bel, Dulce Papy-García, Rosana N Chehín, Patrick P Michel, Rita Raisman-Vozari
ABSTRACT

: 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-, 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.

MATERIALS
Product Number
Brand
Product Description

Rifampicin quinone, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
(Tyr[SO3H]27)Cholecystokinin fragment 26-33 Amide, ≥97% (HPLC), powder
Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O26:B6, ≥10,000 EU/mg, purified by phenol extraction
Supelco
Poly(ethyleneimine) solution, analytical standard, 50 % (w/v) in H2O
Rifampicin, European Pharmacopoeia (EP) Reference Standard