α-Linolenic acid induces clearance of Tau seed via Actin-remodeling in Microglia

Abstract Background Tau seeds exhibit a detrimental role in the spread of disease in Alzheimer’s disease. These species are found to be neurotoxic and activate microglia. However, the activation of microglia in pro-inflammatory response further elevates neurodegeneration. Omega-3 dietary fatty acids, on the other hand; exert an anti-inflammatory response by microglia. Along with the receptor expression, omega-3 fatty acids influence various important cellular functions. The role of omega-3 fatty acids on actin remodeling, which is the basis of cellular functions such as migration and phagocytosis is not known. Here in this study, we focus on effect of dietary supplement of ALA on extracellular Tau internalization and assisted actin polymerization for the process. ALA is found to induce membrane ruffling and phagocytic cup formation along with cytoskeletal rearrangement to induce lamellipodia and filopodia at the front end to move forward and assist the cell to identify the target. ALA is observed to promote the internalization of Tau and necessary actin remodeling for phagocytosis. Methods α-Linolenic (ALA) acid has been used for the study. ALA was dissolved in 100% ethanol and solubilized at 50°C for 2 hours. The human Tau aggregates was prepared in vitro for the internalization study in microglia in presence of α-Linolenic acids (ALA) via fluorescence microscopy with Apotome. The studied the role α-Linolenic acids (ALA) actin remodeling in cellular processes in presence of Tau seed. The study of actin structures lamellipodia, filopodia, and membrane ruffling along with Iba-1 and Arp2/3 complex was observed on ALA exposure. Results Extracellular Tau species are found to internalize more presence of ALA in microglia. The extensive polarization and migration was observed as indicated by extensive lamellipodia and filopodia formation. The formation of extensive actin branching in lamellipodia and membrane ruffling was studied with the help of ARP2/3 complex for nucleating actin network. The high density of ARP2/3 complex at the leading ends of migratory microglia confirmed the extensive branching of actin filaments on ALA exposure. Enhanced formation of lamellipodia and filopodia helps in migration and internalization of tau seed. The actin dynamics supports the phagocytosis process. Conclusion Our approach provides the insights of beneficial role of ALA as anti-inflammatory dietary supplement to treat AD. ALA induces internalization of Tau and necessary actin remodeling for phagocytosis.