Title: Multi-Omics Profiling of Endocannabinoid System Remodeling in Aging Alzheimer’s Disease Mice
The endocannabinoid system (ECS) plays a crucial role in regulating brain homeostasis, inflammation, and aging. In this seminar, I will present new findings on how the ECS is altered in Alzheimer’s disease using the 5xFAD mouse model across different ages. By combining targeted lipidomics of endocannabinoid ligands with quantitative proteomics, we identified age- and genotype-dependent changes that point to dysregulation of neuroprotective pathways. Notably, levels of the endocannabinoid-like molecule PEA decreased in parallel with increased expression of its degrading enzyme NAAA in 5xFAD mice. These shifts may contribute to enhanced neuroinflammation and neurodegeneration. Our integrative approach sheds light on the molecular interface between aging, ECS imbalance, and Alzheimer’s pathology. These findings open new directions for therapeutic intervention targeting the ECS in neurodegenerative disease
