01801nas a2200265   4500008004100000022001400041245007700055210006900132260000800201300001100209490000800220520092900228653002201157653001401179653002501193653002901218653002401247653001601271100002901287700002801316700002001344700002601364700003601390856010901426       2019                        eng d  a0003-986100aBaicalein suppresses repeat tau fibrillization by sequestering oligomers0 aBaicalein suppresses repeat tau fibrillization by sequestering o  cOCT  a1081190 v6753 a<p>Alzheimer's disease (AD) is a neurodegenerative disorder caused by protein misfolding, aggregation and accumulation in the brain. A large number of molecules are being screened against these pathogenic proteins but the focus for therapeutics is shifting towards the natural compounds as aggregation inhibitors, mainly due to their minimum adverse effects. Baicalein is a natural compound belonging to the class of flavonoids isolated from the Chinese herb Scutellaria baicalensis. Here we applied fluorescence, absorbance, microscopy, MALDI-TOF spectrophotometry and other biochemical techniques to investigate the interaction between Tau and Baicalein in vitro. We found the aggregation inhibitory properties of Baicalein for the repeat Tau. Overall, the potential of Baicalein in dissolving the preformed Tau oligomers as well as mature fibrils can be of utmost importance in therapeutics for Alzheimer's disease.</p>
10aAlzheimer disease10aBaicalein10aMicrotubule assembly10aPaired helical filaments10aProtein aggregation10atau protein1 aSonawane, Shweta, Kishor1 aBalmik, Abhishek, Ankur1 aBoral, Debjyoti1 aRamasamy, Sureshkumar1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/baicalein-suppresses-repeat-tau-fibrillization-sequestering-oligomers01967nas a2200241   4500008004100000022001400041245008400055210006900139260000900208300001000217490000800227520117000235653002401405653002801429653001401457653002901471653001601500653001601516100001601532700002801548700003601576856011301612       2020                        eng d  a0141-813000aEffect of melatonin on tau aggregation and tau-mediated cell surface morphology0 aEffect of melatonin on tau aggregation and taumediated cell surf  cJUN   a30-390 v1523 a<p>Aggregation of Microtubule-associated protein Tau and its deposition in the form of neurofibrillary tangles (NFTs) is one of the pathological hallmarks of Alzheimer's disease (AD). Tau aggregation inhibition has been targeted in various studies including natural compounds and synthetic small molecules. Here, we have studied neurohormone- Melatonin against in vitro Tau aggregation and observed its effect on membrane topology, tubulin network and Tau phosphorylation in Neuro2A and N9 cell lines. The aggregation and conformation of Tau was determined by ThT fluorescence and CD spectroscopy respectively. The morphology of Tau aggregates in presence and absence of Melatonin was studied by transmission electron microscopy. Melatonin was found to reduce the formation of higher order oligomeric structures without affecting the overall aggregation kinetics of Tau. Melatonin also modulates and helps to maintain membrane morphology, independent on tubulin network as evidenced by FE-SEM and immunofluorescence analysis. Overall, Melatonin administration shows mild anti-aggregation and cytoprotective effects. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aAlzheimer's disease10aCell surface morphology10amelatonin10aPaired helical filaments10atau protein10aTauopathies1 aDas, Rashmi1 aBalmik, Abhishek, Ankur1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/effect-melatonin-tau-aggregation-and-tau-mediated-cell-surface-morphology02066nas a2200277   4500008004100000022001400041245010400055210006900159260000800228300001100236490000900247520113900256653002401395653001901419653001401438653002901452653001601481653001601497100002801513700001601541700001601557700002801573700002601601700003601627856012501663       2020                        eng d  a0304-416500aMelatonin interacts with repeat domain of Tau to mediate disaggregation of paired helical filaments0 aMelatonin interacts with repeat domain of Tau to mediate disaggr  cMAR  a1294670 v18643 a<p>Tau is the major neuronal protein involved in the stabilization of microtubule assembly. In Alzheimer's disease, Tau self-assembles to form intracellular protein aggregates which are toxic to cells. Various methods have been tried and tested to restrain the aggregation of Tau. Most of the agents tested for this purpose have limitations in their effectiveness and availability to neuronal cells. We have tested melatonin, a neurohormone secreted by pineal gland and a well-known anti-oxidant, for its ability to interact with the repeat domain of Tau using ITC and NMR. In aggregation inhibition and disaggregation studies of repeat Tau, melatonin was found to modulate the aggregation propensity of repeat Tau at a concentration of 5000 mu M and was more effective in dissolving preformed aggregates rather than acting as an aggregation inhibitor. However, there were no major conformational changes in Tau in presence of melatonin as observed by CD spectroscopy. On the basis of our findings, we are proposing a mechanism by which melatonin can interact with the repeat domain of Tau and exhibit its disaggregation effect.</p>
10aAlzheimer's disease10aDisaggregation10amelatonin10aPaired helical filaments10atau protein10aTauopathies1 aBalmik, Abhishek, Ankur1 aDas, Rashmi1 aDangi, Abha1 aGorantla, Nalini, Vijay1 aMarelli, Udaya, Kiran1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/melatonin-interacts-repeat-domain-tau-mediate-disaggregation-paired-helical-filaments