Pro-resolving lipid mediators and neuronal injury

GABRIELA A. SALVADOR

Mendoza

Simposio; Frontiers in Biosciences- France- Argentine-Group; 2023

UN Cuyo-Teresa Damiani

Neutral lipids and specialized pro-resolving mediators: Friends and foes in neurotoxicity.s The loss of dopaminergic neurons in midbrain is a pathognomonic sign of Parkinson´s disease. We found that neuronal challenge with the pesticide Maneb triggers neutral lipid disturbances. Depending on neuronal injury level, lipid droplet increase can act as either protective against damage or as a promoter of cellular death. In addition, Maneb, a ferroptosis inducer associated with Parkinsonism, triggers an imbalance in arachidonic acid (AA) and docosahexaenoic acid (DHA) content both in neurons and astrocytes. As a response to Maneb challenge, neurons and astrocytes are able to activate AA- and DHA-dependent resolution pathways to mitigate pro-inflammatory signaling and promote cell survival. The inflammation/resolution balance is governed by a plethora of specialized pro-resolving lipid mediators that act as ligands of the GPCR receptor FPR2/ALX. Pro-resolving lipid mediators are mainly synthetized by lipoxygenases from AA and DHA. We also demonstrated that neurons and astrocytes secrete lipid ligands for FPR2/ALX-mediated resolution in response to Maneb toxicity. Keywords: neutral lipids, ferroptosis, specialized pro-resolving lipid mediators, neurotoxicityFunding: CONICET, ANPCyT, PGI-UNS