DF3016A induces increased BDNF transcription in ischemic neuroinflammation injury
Marta Grannonico1, Laura Brandolini2, Giustino Varrassi3
1Department of Biology, University of Virginia, Charlottesville, VA, USA.
Abstract:
C5a is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. DF3016A is a novel potent and selective C5a receptor (C5aR) inhibitor that crosses the blood-brain barrier (BBB) and may have pharmacological properties. We have previously demonstrated a protective effect of DF3016A on injured primary cortical neurons by oxygen-glucose deprivation-reoxygenation (OGD/R) model to mimic the neuroinflammatory process. Here, we investigated the molecular pathway and factors involved in the neuroprotection previously reported. Our findings show that DF3016A protects against the neuroinflammatory insult by activating brain-derived neurotrophic factor (BDNF) transcription pathway, which involves methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132) regulatory factors, both required in nociceptive signaling and neuroinflammation. Further in vivo investigations will confirm the functionality of the DF3016A molecule as a therapeutic resource in neuroinflammation and pain injuries.
Insights
DF3016A, a C5a receptor inhibitor, protects neurons by activating brain-derived neurotrophic factor (BDNF) transcription. This mechanism involves methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132), offering potential for neuroinflammation and pain therapies.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- C5a is a key mediator in neuroinflammation and pain.
- DF3016A is a novel C5a receptor (C5aR) inhibitor that penetrates the blood-brain barrier (BBB).
- Previous studies indicated DF3016A's neuroprotective effects in an oxygen-glucose deprivation-reoxygenation (OGD/R) model.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying DF3016A's neuroprotection.
- To identify key regulatory factors involved in DF3016A-mediated neuroprotection.
Main Methods:
- Investigated the molecular pathways affected by DF3016A in a neuronal injury model.
- Analyzed the involvement of brain-derived neurotrophic factor (BDNF) transcription.
- Examined the roles of methyl CpG-binding protein 2 (MeCP2) and microRNA-132 (miR-132).
Main Results:
- DF3016A demonstrated neuroprotection against inflammatory insults.
- Neuroprotection was mediated by the activation of the BDNF transcription pathway.
- MeCP2 and miR-132 were identified as crucial regulatory factors in this pathway.
Conclusions:
- DF3016A exerts neuroprotection by modulating the MeCP2/miR-132/BDNF axis.
- These findings highlight DF3016A's potential as a therapeutic agent for neuroinflammation and pain.
- Further in vivo studies are warranted to confirm its therapeutic efficacy.
More Related Videos
13:46An Improved Protocol to Purify and Directly Mono-Biotinylate Recombinant BDNF in a Tube for Cellular Trafficking Studies in Neurons
Published on: July 11, 2020
05:40AAV Systems and Mouse Models for Investigating Ectopic Expression of Neurod1 in Transduced Cells at Subacute and Chronic Times Post-Ischemic Stroke
Published on: November 29, 2024