The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury

• DOI: 10.1007/s12640-019-00026-w
• Publication Date: 2019-04-05T16:04:30Z
• Authors: Laura Brandolini; Marta Grannonico; Gianluca Bianchini; Alessia Colanardi; Pierluigi Sebastiani; Antonella Paladini; Alba Piroli; Marcello Allegretti; Giustino Varrassi; Silvia Di Loreto
• Keywords: C5a receptor

The central nervous system (CNS) constitutively expresses complement (C) membrane receptors and proteins, including the component C5a. This is a crucial terminal effector of C cascade, mostly involved in pain neuroinflammatory conditions. Aberrant activation C5a protein its receptor C5aR has been reported to play critical role neurodegenerative diseases, with important clinical consequences. Here we have investigated effects DF3016A, novel selective antagonist, able penetrate blood-brain barrier (BBB), on cortical neurons exposed oxygen-glucose deprivation-reoxygenation (OGD/R), neuroinflammation-related process. We demonstrated that mild ischemic insult induces an early upregulation associated over-production pro-inflammatory cytokines over-expression transcriptional regulatory factor miR-181. Furthermore, report first experimental evidence effect modulating C5a, model injury. Interestingly, DF3016A protects neuronal viability by restoring intracellular calcium levels, thus opposing increase cytokine levels miR-181 expression. Based our results, suggest antagonist promoting protective against OGD/R-induced damage could be new therapeutic approach controlling CNS