02109nas a2200217   4500008004100000022001400041245009700055210006900152260000800221300001200229490000800241520134500249653001401594653001401608653001901622653003201641653003101673100003601704700002801740856012301768       2021                        eng d  a0306-452200aImplications of valosin-containing protein in promoting autophagy to prevent tau aggregation0 aImplications of valosincontaining protein in promoting autophagy  cNOV  a125-1340 v4763 aand cellular degradative mechanisms modulate Tau aggregation. During aging and neu-rodegenerative disorders, the cellular proteostasis is disturbed due to impaired protective mechanisms. This results in accumulation of aberrant Tau aggregates in the neuron that leads to microtubule destabilization and neuronal degeneration. The intricate mechanisms to prevent Tau aggregation involve chaperones, autophagy, and proteasomal system have gained main focus about concerning to therapeutic intervention. However, the thor-ough understanding of other key proteins, such as Valosin-containing protein (VCP), is limited. In various neu-rodegenerative diseases, the chaperone-like activity of VCP is involved in preventing protein aggregation and mediating the degradation of aberrant proteins by proteasome and autophagy. In the case of Tau aggregation associated with Alzheimer's disease, the importance of VCP is poorly understood. VCP is known to co-localize with Tau, and alterations in VCP cause aberrant accumulation of Tau. Nevertheless, the direct mechanism of VCP in altering Tau aggregation is not known. Hence, we speculate that VCP might be one of the key modulators in preventing Tau aggregation and can disintegrate Tau aggregates by directing its clearance by autophagy. = 2021 IBRO. Published by Elsevier Ltd. All rights reserved.10aAutophagy10asegregase10aTau aggregates10aUbiquitin-proteasome system10avalosin-containing protein1 aChinnathambi, Subashchandrabose1 aGorantla, Nalini, Vijay  uhttps://library.ncl.res.in/content/implications-valosin-containing-protein-promoting-autophagy-prevent-tau-aggregation02075nas a2200229   4500008004100000022001400041245011200055210006900167260000800236300001100244490000900255520129500264653002501559653001401584653001401598653001301612653001901625100003601644700001601680700002601696856012301722       2023                        eng d  a0167-488900aTau aggregates improve the Purinergic receptor P2Y12-associated podosome rearrangements in microglial cells0 aTau aggregates improve the Purinergic receptor P2Y12associated p  cJUN  a1194770 v18703 a<p>
	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; 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.</p>
10aAlzheimer `s disease10aFilopodia10amicroglia10aPodosome10aTau aggregates1 aChinnathambi, Subashchandrabose1 aDas, Rashmi1 aDesale, Smita, Eknath  uhttps://library.ncl.res.in/content/tau-aggregates-improve-purinergic-receptor-p2y12-associated-podosome-rearrangements