α-Linolenic acid modulates phagocytosis of extracellular Tau and induces microglial migration

Abstract

BackgroundSeeding effect of extracellular Tau species is an emerging aspect to study the Tauopathies in Alzheimer's disease. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. Omega-3 fatty acids are known to exert the anti-inflammatory property to microglia by modulating cell membrane compositions. The immunomodulatory function of omega-3 fatty acids exerts anti-inflammatory property to microglia. Owing to the imparted anti-inflammatory nature enhance phagocytosis and increased migration property has been observed in microglia. The dietary omega-3 fatty acids are found to change the lipid composition of the cell membrane that predominated many signaling cascade and by modulating specific receptor response. Thus the omega-3 fatty acids influence microglial response in Tauopathy. MethodsN9 microglia cells were exposed to extracellular full-length Tau monomer and aggregates along with ALA (α-Linolenic acid) to study the internalization of exposed Tau. The degradation of internalized Tau studied with the endosomal markers Rab5 and Rab7. The final degradation step in phagocytosis has been studied with LAMP-2A as lysosomal markers. The changes in the rate of migration of microglia were Author's information Affiliations

G-Protein coupled Purinergic P2Y12 receptor interacts and internalizes TauRD-mediated by membrane-associated actin cytoskeleton remodelling in microglia

“…The dietary fatty acids are playing a significant role in microglial activation and polarization (41). α-linolenic acid treatment is observed to promote the clearance of Tau seeds by enhanced microglial activation, phagocytosis via actin remodelling and degradation of internalized Tau by endosome-lysosome mediated pathway (42,43). Also, a novel antibody targeting Tau RD oligomers can block the intracellular Tau aggregation and also induces cellular uptake-clearance via lysosomal pathway in N2A cell model (44).…”