Exploring the effects of annexin A1 interactions with NLRP3 in an ex vivo model of Alzheimer's disease: unravelling the dynamics of neuroinflammation and potential therapeutic implications

• Grant number: 24/05491-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: December 01, 2024
• End date: November 30, 2025
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Luiz Philipe de Souza Ferreira
• Supervisor: Claudia Alexandra dos Santos Valente de Castro
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Universidade de Lisboa, Portugal
• Associated to the scholarship: 21/00270-4 - Role of the protein Annexin A1 in the experimental model of Parkinsons Disease, BP.DD

Abstract

Introduction: The human genome encodes 12 annexins, including annexin A1 (AnxA1), knownfor its role in inflammation and immune regulation. Previous research indicates theneuroprotective properties of AnxA1 and its N-terminal peptide, Ac2-26, in promoting a proresolving response in neurological diseases. AnxA1 interacts with the NLRP3 inflammasome(NLRP3), forming a pro-resolution regulatory axis in the peripheral inflammatorymicroenvironment, but this interplay has been scarcely explored in the central nervous system.Objectives: To investigate the interactions of AnxA1 and NLRP3 in an ex vivo model ofAlzheimer's disease. This includes exploring the effect of Ac2-26 on NLRP3 pathway in neurons,astrocytes and microglia.Methods: Acute hippocampal slices from 7-8-week-old Sprague-Dawley rats will be distributedin an incubation plate and exposed to 200 nM of A² oligomers (A²olig) and 25 nM of okadaic acid(OKA), an inhibitor of phosphatase 2A (PP2A), that promotes Tau phosphorylation. The effectsof Ac2-26 upon A²olig/pTau-mediated events will then be investigated.After completing the experiments, slices will be processed for western blotting andimmunohistochemistry assays and the medium will be collected and frozen for Enzyme LinkedImmunosorbent assays. This experimental approach aims to unravel the AnxA1-NLRP3 axis inneurodegenerative conditions.