<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chinnathambi, Subashchandrabose</style></author><author><style face="normal" font="default" size="100%">Das, Rashmi</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Microglia degrade Tau oligomers deposit via purinergic P2Y12-associated podosome and filopodia formation and induce chemotaxis</style></title><secondary-title><style face="normal" font="default" size="100%">Cell and Bioscience</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Filopodia</style></keyword><keyword><style  face="normal" font="default" size="100%">microglia</style></keyword><keyword><style  face="normal" font="default" size="100%">migration</style></keyword><keyword><style  face="normal" font="default" size="100%">Podosome</style></keyword><keyword><style  face="normal" font="default" size="100%">Tau Oligomers</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">MAY</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">13</style></volume><pages><style face="normal" font="default" size="100%">95</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	BackgroundTau protein forms neurofibrillary tangles and becomes deposited in the brain during Alzheimer's disease (AD). Tau oligomers are the most reactive species, mediating neurotoxic and inflammatory activity. Microglia are the immune cells in the central nervous system, sense the extracellular Tau via various cell surface receptors. Purinergic P2Y12 receptor can directly interact with Tau oligomers and mediates microglial chemotaxis via actin remodeling. The disease-associated microglia are associated with impaired migration and express a reduced level of P2Y12, but elevate the level of reactive oxygen species and pro-inflammatory cytokines.ResultsHere, we studied the formation and organization of various actin microstructures such as-podosome, filopodia and uropod in colocalization with actin nucleator protein Arp2 and scaffold protein TKS5 in Tau-induced microglia by fluorescence microscopy. Further, the relevance of P2Y12 signaling either by activation or blockage was studied in terms of actin structure formations and Tau deposits degradation by N9 microglia. Extracellular Tau oligomers facilitate the microglial migration via Arp2-associated podosome and filopodia formation through the involvement of P2Y12 signaling. Similarly, Tau oligomers induce the TKS5-associated podosome clustering in microglial lamella in a time-dependent manner. Moreover, the P2Y12 was evidenced to localize with F-actin-rich podosome and filopodia during Tau-deposit degradation. The blockage of P2Y12 signaling resulted in decreased microglial migration and Tau-deposit degradation.ConclusionsThe P2Y12 signaling mediate the formation of migratory actin structures like- podosome and filopodia to exhibit chemotaxis and degrade Tau deposit. These beneficial roles of P2Y12 in microglial chemotaxis, actin network remodeling and Tau clearance can be intervened as a therapeutic target in AD.&lt;/p&gt;
</style></abstract><issue><style face="normal" font="default" size="100%">1</style></issue><work-type><style face="normal" font="default" size="100%">Article</style></work-type><custom3><style face="normal" font="default" size="100%">&lt;p&gt;
	Foreign&lt;/p&gt;
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	9.548&lt;/p&gt;
</style></custom4></record><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Chinnathambi, Subashchandrabose</style></author><author><style face="normal" font="default" size="100%">Das, Rashmi</style></author><author><style face="normal" font="default" size="100%">Desale, Smita Eknath</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Tau aggregates improve the Purinergic receptor P2Y12-associated podosome rearrangements in microglial cells</style></title><secondary-title><style face="normal" font="default" size="100%">Biochimica Et Biophysica Acta-Molecular Cell Research</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Alzheimer `s disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Filopodia</style></keyword><keyword><style  face="normal" font="default" size="100%">microglia</style></keyword><keyword><style  face="normal" font="default" size="100%">Podosome</style></keyword><keyword><style  face="normal" font="default" size="100%">Tau aggregates</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2023</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JUN</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">1870</style></volume><pages><style face="normal" font="default" size="100%">119477</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;
	Alzheimer's disease (AD) is a progressive neurodegenerative disease that is associated with protein misfolding, plaque accumulation, neuronal dysfunction, synaptic loss, and cognitive decline. The pathological cascade of AD includes the intracellular Tau hyperphosphorylation and its subsequent aggregation, extracellular Amyloid-&amp;amp; beta; plaque formation and microglia-mediated neuroinflammation. The extracellular release of aggregated Tau is sensed by surveilling microglia through the involvement of various cell surface receptors. Among all, purinergic P2Y12R signaling is involved in microglial chemotaxis towards the damaged neurons. Microglial migration is highly linked with membrane-associated actin remodeling leading to the phagocytosis of extracellular Tau species. Here, we studied the formation of various actin structures such as podosome, lamellipodia and filopodia, in response to extracellular Tau monomers and aggregates. Microglial podosomes are colocalized with actin nucleator protein WASP, Arp2 and TKS5 adaptor protein during Tau-mediated migration. Moreover, the P2Y12 receptors were associated with F-actin-rich podosome structures, which signify the potential of Tau aggregates in microglial chemotaxis through the involvement of actin remodeling.&lt;/p&gt;
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	Foreign&lt;/p&gt;
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	5.1&lt;/p&gt;
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