Sajad Shahbazi

Title : A novel NF-Kappa B silencer: benzo-dioxole-piperamide and its role as an anti-neuroinflammatory agent

Abstract:

Background: NF-kB contributes to the biosynthesis of various chemokines, cytokines, andenzymes. It plays many crucial roles in the upstream neuroinflammatory pathways. Thephosphorylation of Ser32 and 36 residues of IkB subunit leads to disruption of the bind between NF-kB complex protein and the inhibitory subunit (IkB). The mentioned process activates the NF-kB complex to shift into the nucleus and binds to the chromosomal DNA. One of the mostprominent targets to regulate the translocation of the NF-kB complex into the nucleus is the IKK-β enzyme.  Inhibitors may bind directly to the active site of the IKK-β enzyme or suppress the geneexpression of the IKK-β enzyme and protect the integrity of the NF-kB complex and keep it in the inactive form inside cytosol

Methodology: In the present study, we developed a novel NF-kB inhibitor encoded (D5) andinvestigated the efficacy of our druggable compound through various in silico, in vitro, and insitu tests. We have investigated the impact of D5 on the gene expression of the IKK-β enzyme using rt-PCR. The enzymatic function of IKK-β was indirectly monitored using a monoclonal anti-phospho-IkB-α (S32)  to tract the radical phospho-IkB in the cytosol of microglial and astrocytic cells using western blot and immunocytochemistry techniques. The structuralinhibition of IKK-β by D5 and pharmacological properties of D5 were evaluated using in silicodrug discovery tools such as Schrodinger suite 2011 and Accelrys discovery studio ver. 2.5. The statistical analysis was performed using Microsoft Exel 2007.

Results: The results indicated that D5 inhibited the IKK-β enzyme in both genome andproteome. D5 demonstrated a significant reduction of the radical phospho-IkB-α in the cytosol ofhuman microglia and astrocytes. 

Conclusion: the brilliant protective effect on the NF-kB complex, the great pharmacological properties for oral administration, and lack of toxicity, made D5 the most prominent inhibitor of the NF-kB pathway for further studies on developing a potent anti-inflammatory and anti-neuroinflammatory agent.                             

Biography:

Dr. Sajad Shahbazi was awarded his Ph.D. in the field of Biotechnology from Panjab University, India (2018). He started his work as a Special GR and postdoctoral fellow at the Nencki Institute of Experimental Biology to investigate a novel technology and methodology to assay matrix metalloproteinase in the inflammatory process in the brain and its role in neuronal plasticity. During his scientific journey from his master's to his current scientific position, he has published various papers in several reputed journals. He has also been awarded several scientific rewards. The research interest of Dr. Sajad Shahbazi is to investigate drug-target interaction as well as a study of the genomics and proteomics leading to detect, design, and chemically or biologically synthesized druggable molecules for various neuronal disorders for further in vitro and in vivo studies. He is eager to investigate the immunomodulatory roles of phytochemicals and their semisynthetic or synthetic derivatives. Subsequently, validate their efficacies through various in vivo studies.