<?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%">Das, Rashmi</style></author><author><style face="normal" font="default" size="100%">Balmik, Abhishek Ankur</style></author><author><style face="normal" font="default" size="100%">Chinnathambi, Subashchandrabose</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Melatonin reduces GSK3 beta-mediated tau phosphorylation, enhances Nrf2 nuclear translocation and anti-inflammation</style></title><secondary-title><style face="normal" font="default" size="100%">ASN Neuro</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Alzheimer&amp;\#8217</style></keyword><keyword><style  face="normal" font="default" size="100%">Anti-inflammatory</style></keyword><keyword><style  face="normal" font="default" size="100%">GSK3&amp;\#946</style></keyword><keyword><style  face="normal" font="default" size="100%">melatonin</style></keyword><keyword><style  face="normal" font="default" size="100%">microglia</style></keyword><keyword><style  face="normal" font="default" size="100%">neurodegeneration</style></keyword><keyword><style  face="normal" font="default" size="100%">Nrf2</style></keyword><keyword><style  face="normal" font="default" size="100%">s disease</style></keyword><keyword><style  face="normal" font="default" size="100%">Tau hyperphosphorylation</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">DEC</style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">12</style></volume><pages><style face="normal" font="default" size="100%">1759091420981204</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 is a neuropathological condition with abnormal accumulation of extracellular Amyloid-beta plaques and intracellular neurofibrillary tangles of Microtubule-associated protein Tau (Tau) in the brain. In pathological conditions, Tau undergoes post-translational modifications such as hyperphosphorylation by the activity of cellular kinases, which eventually leads to protein aggregation in neurons. Melatonin is a neuro-hormone that is mainly secreted from the pineal gland and functions to modulate the cellular kinases. In our study, we have checked the neuroprotective function of Melatonin by MTT and LDH assay, where Melatonin inhibited the Tau aggregates-mediated cytotoxicity and membrane leakage in Neuro2A cells. The potency of Melatonin has also been studied for the quenching of intracellular reactive oxygen species level by DCFDA assay and caspase 3 activity. Melatonin was shown to reduce the GSK3 beta mRNA and subsequent protein level as well as the phospho-Tau level (pThr181 and pThr212-pSer214) in okadaic acid-induced Neuro2A cells, as observed by western blot and immunofluorescence assay. Further, Melatonin has increased the cellular Nrf2 level and its nuclear translocation as an oxidative stress response in Tauopathy. The Melatonin was found to induce pro- and anti-inflammatory cytokines levels in N9 microglia. The mRNA level of cellular kinases such as as-GSK3 beta, MAPK were also studied by qRT-PCR assay in Tau-exposed N9 and Neuro2A cells. The immunomodulatory effect of Melatonin was evident as it induced IL-10 and TGF-beta cytokine levels and activated MAP3K level in Tau-exposed microglia and neurons, respectively. Melatonin also downregulated the mRNA level of pro-inflammatory markers, IL-1 beta and Cyclooxygenase-2 in N9 microglia. Together, these findings suggest that Melatonin remediated the cytokine profile of Tau-exposed microglia, reduced Tau hyperphosphorylation by downregulating GSK3 beta level, and alleviated oxidative stress via Nrf2 nuclear translocation.&lt;/p&gt;
</style></abstract><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;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;4.167&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%">Das, Rashmi</style></author><author><style face="normal" font="default" size="100%">Balmik, Abhishek Ankur</style></author><author><style face="normal" font="default" size="100%">Chinnathambi, Subashchandrabose</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia</style></title><secondary-title><style face="normal" font="default" size="100%">Journal of Neuroinflammation</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Actin</style></keyword><keyword><style  face="normal" font="default" size="100%">activation</style></keyword><keyword><style  face="normal" font="default" size="100%">Alzheimer's disease</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%">neurodegeneration</style></keyword><keyword><style  face="normal" font="default" size="100%">Tau Oligomers</style></keyword><keyword><style  face="normal" font="default" size="100%">Tauopathy</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2020</style></year><pub-dates><date><style  face="normal" font="default" size="100%">JAN </style></date></pub-dates></dates><volume><style face="normal" font="default" size="100%">17</style></volume><pages><style face="normal" font="default" size="100%">10</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Background Alzheimer's disease is associated with the accumulation of intracellular Tau tangles within neurons and extracellular amyloid-beta plaques in the brain parenchyma, which altogether results in synaptic loss and neurodegeneration. Extracellular concentrations of oligomers and aggregated proteins initiate microglial activation and convert their state of synaptic surveillance into a destructive inflammatory state. Although Tau oligomers have fleeting nature, they were shown to mediate neurotoxicity and microglial pro-inflammation. Due to the instability of oligomers, in vitro experiments become challenging, and hence, the stability of the full-length Tau oligomers is a major concern. Methods In this study, we have prepared and stabilized hTau40(WT) oligomers, which were purified by size-exclusion chromatography. The formation of the oligomers was confirmed by western blot, thioflavin-S, 8-anilinonaphthaalene-1-sulfonic acid fluorescence, and circular dichroism spectroscopy, which determine the intermolecular cross-beta sheet structure and hydrophobicity. The efficiency of N9 microglial cells to phagocytose hTau40(WT) oligomer and subsequent microglial activation was studied by immunofluorescence microscopy with apotome. The one-way ANOVA was performed for the statistical analysis of fluorometric assay and microscopic analysis. Results Full-length Tau oligomers were detected in heterogeneous globular structures ranging from 5 to 50 nm as observed by high-resolution transmission electron microscopy, which was further characterized by oligomer-specific A11 antibody. Immunocytochemistry studies for oligomer treatment were evidenced with A11(+) Iba1(high) microglia, suggesting that the phagocytosis of extracellular Tau oligomers leads to microglial activation. Also, the microglia were observed with remodeled filopodia-like actin structures upon the exposure of oligomers and aggregated Tau. Conclusion The peri-membrane polymerization of actin filament and co-localization of Iba1 relate to the microglial movements for phagocytosis. Here, these findings suggest that microglia modified actin cytoskeleton for phagocytosis and rapid clearance of Tau oligomers in Alzheimer's disease condition.&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;
</style></custom3><custom4><style face="normal" font="default" size="100%">&lt;p&gt;5.793&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%">Balmik, Abhishek Ankur</style></author><author><style face="normal" font="default" size="100%">Sonawane, Shweta Kishor</style></author><author><style face="normal" font="default" size="100%">Chinnathambi, Subashchandrabose</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Extracellular HDAC6 ZnF UBP domain modulates the actin network and post-translational modifications of Tau</style></title><secondary-title><style face="normal" font="default" size="100%">Cell Communication and Signaling</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Actin</style></keyword><keyword><style  face="normal" font="default" size="100%">Cytoskeleton</style></keyword><keyword><style  face="normal" font="default" size="100%">HDAC6</style></keyword><keyword><style  face="normal" font="default" size="100%">Microtubule</style></keyword><keyword><style  face="normal" font="default" size="100%">neurodegeneration</style></keyword><keyword><style  face="normal" font="default" size="100%">Phosphorylation</style></keyword><keyword><style  face="normal" font="default" size="100%">Podonut</style></keyword><keyword><style  face="normal" font="default" size="100%">Podosomes</style></keyword><keyword><style  face="normal" font="default" size="100%">Tau</style></keyword><keyword><style  face="normal" font="default" size="100%">Tauopathies</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</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%">19</style></volume><pages><style face="normal" font="default" size="100%">49</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Background: Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease (AD) and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. Histone deacetylase-6 (HDAC6) plays an important role in aggresome formation, where it recruits polyubiquitinated aggregates to the motor protein dynein. Methods: Here, we have studied the effects of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3 beta regulation and cytoskeletal organization in neuronal cells by immunocytochemical analysis. This analysis reveals that the cell exposure to the UBP-type zinc finger domain of HDAC6 (HDAC6 ZnF UBP) can modulate Tau phosphorylation and actin cytoskeleton organization. Results: HDAC6 ZnF UBP treatment to cells did not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting the role of this domain in actin re-organization. Also, HDAC6 ZnF UBP treatment caused increase in nuclear localization of ApoE and tubulin localization in microtubule organizing centre (MTOC). Therefore, our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases. Upon HDAC6 ZnF UBP treatment, inactive phosphorylated form of GSK-3 beta increases without any change in total GSK-3 beta level. Conclusions: HDAC6 ZnF UBP was found to be involved in cytoskeletal re-organization by modulating actin dynamics and tubulin localization. Overall, our study suggests that ZnF domain of HDAC6 performs various regulatory functions apart from its classical function in aggresome formation in protein misfolding diseases.&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;</style></custom3><custom4><style face="normal" font="default" size="100%">5.712</style></custom4></record></records></xml>