02050nas a2200229   4500008004100000022001400041245009500055210006900150260000900219300001200228490000800240520126000248653002401508653002401532653002001556653001901576653001701595100002101612700002501633700003601658856012601694       2020                        eng d  a0141-813000aCobalt-based metal complexes prevent repeat tau aggregation and nontoxic to neuronal cells0 aCobaltbased metal complexes prevent repeat tau aggregation and n  cJUN   a171-1790 v1523 a<p>Alzheimer's disease (AD) is a fatal neurodegenerative disorder with an alarming increase in the death rate every year. AD is characterised by an aberrant accumulation of proteins in the form of aggregates. The axonal microtubule-associated protein Tau and arnyloid-beta undergo structural transition to beta-sheet rich structure and form aggregates in neuronal soma as well as in the extracellular region. The loss of Tau from microtubules leads to the disintegration of axon and causing neuronal degeneration. This led to the development of effective drugs against AD, to prevent Tau aggregation. Here, we synthesized and screen metal-based complexes to prevent Tau protein aggregation. ThS fluorescence and TEM suggested the role of synthetic cobalt complexes in inhibiting Tau aggregation. CD spectroscopy showed that these complexes prevented conformational changes in Tau to beta-sheet. CBMCs were not toxic at lower concentrations and formed non-toxic Tau species. L1 and L2 prevented membrane leakage: whereas, higher concentrations of L3 caused membrane leakage as observed by LDH release assay. The overall results indicate the synthetic cobalt complexes to be a promising molecule against AD. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aAlzheimer's disease10aCobalt-based metals10aTau Aggregation10aTau inhibition10aTau toxicity1 aGorantla, Nalini1 aBalaraman, Ekambaram1 aChinnathambi, Subashchandrabose  uhttp://library.ncl.res.in/content/cobalt-based-metal-complexes-prevent-repeat-tau-aggregation-and-nontoxic-neuronal-cells02929nas a2200217   4500008004100000245010400041210006900145260000900214300000700223490000700230520216300237653002402400653001402424653002002438653001902458653001802477100002902495700002602524700003602550856012502586       2021                        eng d00aBaicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation0 aBaicalein inhibits heparininduced Tau aggregation by initializin  cFEB   a160 v193 a<p>Background: Amyloid aggregate deposition is the key feature of Alzheimer's disease. The proteinaceous aggregates found in the afflicted brain are the intra-neuronal neurofibrillary tangles formed by the microtubule-associated protein Tau and extracellular deposits, senile plaques, of amyloid beta (A beta) peptide proteolytically derived from the amyloid precursor protein. Accumulation of these aggregates has manifestations in the later stages of the disease, such as memory loss and cognitive inabilities originating from the neuronal dysfunction, neurodegeneration, and brain atrophy. Treatment of this disease at the late stages is difficult, and many clinical trials have failed. Hence, the goal is to find means capable of preventing the aggregation of these intrinsically disordered proteins by inhibiting the early stages of their pathological transformations. Polyphenols are known to be neuroprotective agents with the noticeable potential against many neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Prion diseases. Methods: We analyzed the capability of Baicalein to inhibit aggregation of human Tau protein by a multifactorial analysis that included several biophysical and biochemical techniques. Results: The potency of Baicalein, a polyphenol from the Scutellaria baicalensis Georgi, against in vitro Tau aggregation and PHF dissolution has been screened and validated. ThS fluorescence assay revealed the potent inhibitory activity of Baicalein, whereas ANS revealed its mechanism of Tau inhibition viz. by oligomer capture and dissociation. In addition, Baicalein dissolved the preformed mature fibrils of Tau thereby possessing a dual target action. Tau oligomers formed by Baicalein were non-toxic to neuronal cells, highlighting its role as a potent molecule to be screened against AD. Conclusion: In conclusion, Baicalein inhibits aggregation of hTau40 by enhancing the formation of SDS-stable oligomers and preventing fibril formation. Baicalein-induced oligomers do not affect the viability of the neuroblastoma cells. Therefore, Baicalein can be considered as a lead molecule against Tau pathology in AD.</p>
10aAlzheimer's disease10aBaicalein10aTau dissolution10aTau inhibition10aTau Oligomers1 aSonawane, Shweta, Kishor1 aUversky, Vladimir, N.1 aChinnathambi, Subashchandrabose  uhttp://library.ncl.res.in/content/baicalein-inhibits-heparin-induced-tau-aggregation-initializing-non-toxic-tau-oligomer