Validation of novel molecular targets from anti-inflammatory and cytoprotective molecules in neurons

• Grant number: 24/10065-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2024
• End date: July 31, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Agreement: GlaxoSmithKline
• Principal Investigator: Vanessa Olzon Zambelli
• Grantee: Jorge Luiz Dallazen
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Company: Secretaria da Saúde (São Paulo - Estado). Instituto Butantan
• Associated research grant: 20/13139-0 - Centre of Excellence in New Target Discovery, AP.PCPE

Abstract

The in vitro screening of natural and synthetic peptides derived from animal venoms to evaluate their cytoprotective and anti-inflammatory activities has contributed to the discovery of new pharmacological targets and the elucidation of pain and inflammation signaling pathways. Together with chemoproteomics assays, several peptides derived from Lonomia obliqua and Amblyomma cajennense were tested in various cell cultures, including human sensory neurons and chondrocytes. In these cultures, the peptides had as molecular targets mediators that may be involved in the analgesic response, promoting a lower release of excitatory neuropeptides and an increased release of endogenous analgesic mediators. For this, a CRISPR methodology was established and knockout (KO) cells for specific targets were developed. Considering the promising results already obtained, the aim of this project is to evaluate and validate the potential antinociceptive and anti-inflammatory effects of these peptides in experimental models of pain and arthritis in rodents. (AU)