Abstract: Unesterified lipid mediators are bioactive metabolites of polyunsaturated fatty acid oxidation that regulate inflammation and resolution pathways in vivo. In the brain, these bioactive lipids can be inactivated through esterification into phospholipids or neutral lipids. It is not known whether lipid mediator esterification is altered in neurodegenerative brain disorders.
Objective: To understand the role of lipid mediator esterification in neurodegenerative disorders including Multiple Sclerosis and Alzheimer’s disease.
Methods: Free and esterified lipid mediators were measured in postmortem prefrontal cortex of individuals with Multiple Sclerosis or Alzheimer’s disease and compared to their respective controls.
Results: In Multiple Sclerosis, there was an increase in pro-resolving lipid mediators within neutral lipids, whereas in Alzheimer’s disease, a marked reduction in esterified pro-resolving lipid mediators was observed. Minimal changes were seen in the free lipid mediator pool.
Conclusion: This study demonstrates disease-specific dysregulation in the esterification of free lipid mediators involved in inflammation resolution. The findings suggest changes in the turnover and bioavailability of unesterified pro-resolving lipid mediators in neurodegenerative disorders.
