Fig. 2

Lipid mediators influencing phagocytosis in microglia. In Alzheimer’s disease, microglia cells majorly drive neuroinflammation. Microglia cells show pro-inflammatory and anti-inflammatory phenotype depending upon the presence of lipid-mediators, receptors expressed, and cytokine secretion. The classical inflammatory phase is marked by the presence of inflammatory cytokines, whereas alternative activation state, i.e., phagocytic state, shows anti-inflammatory state, which drives the clearance of debris, accumulated proteins, etc. Free fatty acids cleaved from cell membrane through action of phospholipase enzymes are targeted to lipid mediator’s synthesis. These lipid mediators then trigger the type of reaction given by microglia cells. Lipid mediators show response depending upon the type of receptors that they bind to microglia cells. PGD2 and PGJ2 stimulate anti-inflammatory response, and they target microglia through DP-1 receptor and exert its anti-inflammatory response through translocation of nuclear receptor PPAR-γ to nucleus increasing production of anti-inflammatory cytokine IL-10, which resolves chronic inflammation; IL-10 has anti-inflammatory property, which is a key regulator of phagocytic phenotype. The E-series (RvE1, RvE2, RvE3) and D-series (RvD, RvD1, RvD2, RvD3) resolvins synthesized from EPA and DHA are together called as SPM (specialized pre-resolving mediators). Protectins (NPD1) suppresses pro-inflammatory response by blocking IKK (activator of NF-κB) and NF-κB and increasing IKB (inhibitor of kappa B). SPM also regulates translocation of NF-κB into nucleus and successive production of inflammatory cytokine (IL-1β, TNF-α); hence, by blocking the NF-κB pathway, SPMs can resolve inflammatory phase efficiently. SPM increases phagocytosis of apoptotic bodies, which includes Aβ protein. Maresin-1, a DHA-derived lipid mediator, which is one of the SPM, has specialty to drive the polarization of microglia from inflammatory to anti-inflammatory phenotype and imparts tissue regeneration