02930nas a2200217   4500008004100000245010400041210006900145260000900214300000700223490000700230520216300237653002402400653001402424653002002438653001902458653001802477100002902495700002602524700003602550856012602586       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  uhttps://library.ncl.res.in/content/baicalein-inhibits-heparin-induced-tau-aggregation-initializing-non-toxic-tau-oligomer