Journal Article

Baicalein inhibits heparin-induced Tau aggregation by initializing non-toxic Tau oligomer formation

Sonawane, Shweta Kishor, Uversky, Vladimir N., Chinnathambi, Subashchandrabose

2021

Overview

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 (Aβ) 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. 7WG9tgRW_24b19dTX7j1bj Video Abstract

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Alzheimer's disease / Amyloid precursor protein / Animals / Anticoagulants / Atrophy / Baicalein / Biomedical and Life Sciences / Cell Biology / Cell Line, Tumor / Cell Survival - drug effects / Chromatography / Clinical trials / Cognitive ability / Cytokines and Growth Factors / Disease / Escherichia coli - genetics / Fibrils / Flavanones - pharmacology / Heparin / Hypotheses / Life Sciences / Mice / Neuroblastoma / Neuroblastoma cells / Neurodegeneration / Neurodegenerative diseases / Neurofibrillary tangles / Neuroprotection / Neuroprotective agents / Neuroprotective Agents - pharmacology / Oxidative stress / Pathology / Phosphorylation / Polyphenols / Protein Aggregation, Pathological - drug therapy / Protein Aggregation, Pathological - metabolism / Protein Conformation / Protein-Ligand Interactions / Proteins / Reagents / Receptors / Senile plaques / Tau dissolution / Tau inhibition / Tau oligomers / Tau protein / tau Proteins - chemistry / tau Proteins - genetics / tau Proteins - metabolism / β-Amyloid