03275nas a2200229   4500008004100000022001400041245010600055210006900161260000900230300001200239490000800251520249700259653002102756653002402777653001402801653001802815653002102833653001402854100001602868700003602884856012502920       2020                        eng d  a0306-452200aActin-mediated microglial chemotaxis via G-protein coupled purinergic receptor in alzheimer's disease0 aActinmediated microglial chemotaxis via Gprotein coupled puriner  cNOV   a325-3360 v4483 a<p>Alzheimer's disease (AD) is a neurodegenerative disease mainly associated with aging, oxidative stress and genetic mutations. There are two pathological proteins involved in AD; Amyloid-beta peptide and microtubule-associated protein Tau (MAPT). The beta- and gamma-secretase enzyme cleaves the Amyloid precursor protein, which results in the formation of extracellular plaques in brain. While, Tau undergoes hyperphosphorylation and other post-translational modifications (PTMs), which eventually generates Tau oligomers, and intracellular neurofibrillary tangles (NFTs) in neurons. Moreover, the brain-resident glia and infiltrated macrophages elevate the level of CNS inflammation, which trigger the oxidative damage of neuronal circuits by reactive oxygen species (ROS) and Nitric oxide (NO). Microglia is the primary immune cell in the CNS, which is continuously surveilling the neuronal synapses and pathogen invasion. Microglia in the resting state is called `Ramified', which possess long surveilling extensions with a small cell body. But, upon activation, microglia retracts the cellular extensions and transform into round migratory cells, called as `Amoeboid' state. Activated microglia undergoes actin remodeling by forming lamellipodia and filopodia, which directs the migratory axis while podosomes formed are involved in extracellular matrix degradation for invasion. Protein-aggregates in malfunctioning synapses and in CNS milieu can be detected by microglia, which results in its activation and migration. Subsequently, the phagocytosis of synapses leads to the inflammatory burst and memory loss. The extracellular nucleotides released from damaged neurons and the cytokine-chemokine gradients allow the neighboring microglia and macrophages to migrate-infiltrate at the site of neuronal-damage. The ionotropic (P2XR) and metabotropic (P2YR) purinergic receptor recognize extracellular ATP/ADP, which propagates through the intracellular calcium signaling, chemotaxis, phagocytosis and inflammation. The P2Y receptors give `find me' or `eat me' signals to microglia to either migrate or phagocytose cellular debris. Further, the actin cytoskeleton helps microglia to mediate directed chemotaxis and neuronal repair during neurodegeneration. Hence, we aim to emphasize the connection between purinergic signaling and actin-driven mechanical movements of microglia for migration and inflammation in AD. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.</p>
10aactin remodeling10aAlzheimer's disease10amicroglia10aP2Y signaling10apurinergic GPCRs10aTauopathy1 aDas, Rashmi1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/actin-mediated-microglial-chemotaxis-g-protein-coupled-purinergic-receptor-alzheimers02423nas a2200241   4500008004100000022001400041245012900055210006900184260000800253300001200261490000700273520160700280653002101887653001901908653001501927653001401942653001401956653001401970653001801984100001602002700003602018856012702054       2021                        eng d  a1398-921900aMicroglial remodeling of actin network by Tau oligomers, via G protein-coupled purinergic receptor, P2Y12R-driven chemotaxis0 aMicroglial remodeling of actin network by Tau oligomers via G pr  cMAY  a153-1700 v223 a<p>Alzheimer's disease (AD) is associated with age-related neurodegeneration, synaptic deformation and chronic inflammation mediated by microglia and infiltrated macrophages in the brain. Tau oligomers can be released from damaged neurons via various mechanisms such as exosomes, neurotransmitter, membrane leakage etc. Microglia sense the extracellular Tau through several cell-surface receptors and mediate chemotaxis and phagocytosis. The purinergic receptor P2Y12R recently gained interest in neurodegeneration for neuro-glial communication and microglial chemotaxis towards the site of plaque deposition. To understand the effect of extracellular Tau oligomers in microglial migration, the P2Y12R-mediated actin remodeling, reorientation of tubulin network and rate of migration were studied in the presence of ATP. The extracellular Tau species directly interacted with P2Y12R and also induced this purinoceptor expression in microglia. Microglial P2Y12R colocalized with remodeled membrane-associated actin network as a component of migration in response to Tau oligomers. As an inducer of P2Y12R, ATP facilitated the localization of P2Y12R in lamellipodia and filopodia during accelerated microglial migration. The direct interaction of extracellular Tau oligomers with microglial P2Y12R would facilitate the signal transduction in both way, directional chemotaxis and receptor-mediated phagocytosis. These unprecedented findings emphasize that microglia can modulate the membrane-associated actin structure and incorporate P2Y12R to perceive the axis and rate of chemotaxis in Tauopathy.</p>
10aactin remodeling10aAlzheimer&apos10achemotaxis10amicroglia10amigration10as disease10aTau Oligomers1 aDas, Rashmi1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/microglial-remodeling-actin-network-tau-oligomers-g-protein-coupled-purinergic-receptor