The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury. View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04-05

AUTHORS

Laura Brandolini, Marta Grannonico, Gianluca Bianchini, Alessia Colanardi, Pierluigi Sebastiani, Antonella Paladini, Alba Piroli, Marcello Allegretti, Giustino Varrassi, Silvia Di Loreto

ABSTRACT

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

References to SciGraph publications

Journal

TITLE

Neurotoxicity Research

ISSUE

N/A

VOLUME

N/A

Author Affiliations

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12640-019-00026-w

DOI

http://dx.doi.org/10.1007/s12640-019-00026-w

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113261869

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30953275


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