BLOCKING NEUROINFLAMMATION: EVALUATION OF AD-16 MOLECULAR MECHANISMS IN A HUMAN MICROGLIAL CELL LINEAGE

• Grant number: 24/22395-1
• Support Opportunities: Scholarships abroad - Research Internship - Scientific Initiation
• Start date: April 30, 2025
• End date: July 31, 2025
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Luiz Roberto Giorgetti de Britto
• Grantee: Maria Eduarda Bianchetti Goulart
• Supervisor: Cristine Alves da Costa
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), France
• Associated to the scholarship: 23/05618-4 - Assessment of compound AD-16´s possible inibitory action on neuroinflammation in animal model for Parkinson´s Disease, BP.IC

Abstract

Neuroinflammation is an inflammatory response in the central nervous system triggered by various factors such as infections, trauma, toxins, or neurodegenerative diseases like Parkinson's Disease (PD). While it plays a beneficial role in tissue repair and pathogen removal, excessive or chronic neuroinflammation can lead to neurotoxic factor release, tissue damage, and neurodegeneration. Microglia, the brain's resident immune cells, are central to neuroinflammation. Under normal conditions, they support neuronal health, but in diseases like PD, microglia become activated, releasing pro-inflammatory cytokines and damaging factors, contributing to disease progression. A compound, AD-16, was identified in a microglia-based screening for its anti-inflammatory properties. It reduced pro-inflammatory cytokine levels (e.g., IL-1¿, TNF-¿, NO) in LPS-activated microglia and improved lysosomal function, which may enhance microglial clearance of harmful proteins. This project aims to further investigate AD-16's anti-inflammatory effects and therapeutic potential in human microglial HMC3 cell line, by performing assays to quantify nitric oxide (NO) production and several pro and anti-inflammatory cytokines levels, in addition to caspase-1 and caspase-3 activity and proteomic analysis to identify AD-16´s molecular targets. This approach offers a more accurate model for studying the compound's mechanisms, as it better mimics human responses compared to animal models.