02078nas a2200229   4500008004100000022001400041245008100055210006900136260000900205300001200214490000800226520130500234653002501539653002401564653002001588653002101608653002301629100002601652700001801678700003601696856011601732       2021                        eng d  a0141-813000aAlpha-Linolenic acid inhibits Tau aggregation and modulates Tau conformation0 aAlphaLinolenic acid inhibits Tau aggregation and modulates Tau c  cJAN   a687-6930 v1663 a<p>Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-beta, plaques and intracellular neurofibrillary tangles of Tau. Intrinsically disordered protein tau has several interacting partners, which are necessary for its normal functioning. Tau has been shown to interact with various proteins, nucleic acid, and lipids. alpha-Linolenic acid (ALA) a plant-based omega-3 fatty acid has been studied for its role as neuroprotective and beneficial fatty add in the brain. In this study, we are focusing on the ability of ALA to induce spontaneous assembly in tau protein. ALA inhibited the Tau aggregation as indicated by reduced ThS fluorescence kinetics, which indicates no aggregation of Tau. Similarly, SDS-PAGE analysis supported that ALA exposure inhibited the aggregation as no higher-order tau species were observed. Along with its ability to impede the aggregation of Tau, ALA also maintains a native random coiled structure, which was estimated by CD spectroscopy. Finally, TEM analysis showed that the formation of Tau fibrils was found to be discouraged by ALA. Hence, conclusion of the study suggested that ALA profoundly inhibited aggregation of Tau and maintained it's the random-coil structure. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aalpha-linolenic acid10aAlzheimer's disease10aFree fatty adds10aTau conformation10aTau fibrillization1 aDesale, Smita, Eknath1 aDubey, Tushar1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/alpha-linolenic-acid-inhibits-tau-aggregation-and-modulates-tau-conformation02570nas 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