02570nas a2200217   4500008004100000245011000041210006900151260000800220300000700228490000700235520179900242653002102041653002402062653002402086653001702110653002202127653001902149100002602168700003602194856012202230       2021                        eng d00aPhosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer's disease0 aPhosphoinositides signaling modulates microglial actin remodelin  cFEB  a280 v193 a<p>Alzheimer's disease is one of the neurodegenerative diseases, characterized by the accumulation of abnormal protein deposits, which disrupts signal transduction in neurons and other glia cells. The pathological protein in neurodegenerative diseases, Tau and amyloid-P contribute to the disrupted microglial signaling pathways, actin cytoskeleton, and cellular receptor expression. The important secondary messenger lipids i.e., phosphatidylinositols are largely affected by protein deposits of amyloid-beta in Alzheimer's disease. Phosphatidylinositols are the product of different phosphatidylinositol kinases and the state of phosphorylation at D3, D4, and D5 positions of inositol ring. Phosphatidylinositol 3,4,5-triphosphate (PI 3, 4, 5-P3) involves in phagocytic cup formation, cell polarization, whereas Phosphatidylinositol 4,5-bisphosphate (PI 4, 5-P2)-mediates the process of phagosomes formation and further its fusion with early endosome.. The necessary activation of actin-binding proteins such as Rac, WAVE complex, and ARP2/3 complex for the actin polymerization in the process of phagocytosis, migration is regulated and maintained by PI 3, 4, 5-P3 and PI 4, 5-P2. The ratio and types of fatty acid intake can influence the intracellular secondary lipid messengers along with the cellular content of phaphatidylcholine and phosphatidylethanolamine. The Amyloid-beta deposits and extracellular Tau seeds disrupt phosphatidylinositides level and actin cytoskeletal network that hamper microglial-signaling pathways in AD. We hypothesize that being a lipid species intracellular levels of phosphatidylinositol would be regulated by dietary fatty acids. Further we are interested to understand phosphoinositide-based signaling cascades in phagocytosis and actin remodeling.</p>
10aactin remodeling10aAlzheimer's disease10aDietary fatty acids10aPhagocytosis10aPhosphoinositides10aPI3K signaling1 aDesale, Smita, Eknath1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/phosphoinositides-signaling-modulates-microglial-actin-remodeling-and-phagocytosis