Biology subjects

Sonawane, S. K.

Publications and source records attributed to Sonawane, S. K..

3 recordsLinked to original sources

bioRxiv2020

EGCG modulates nuclear formaldehyde-induced Tau phosphorylation in Neuronal cells

Tau hyperphosphorylation is one of the major causes of Alzheimers disease pathology. The abnormal phosphorylation curtails the physiological function of Tau of microtubule stabilization and renders it more prone to aggregation. Apart from its function in the cytoplasm, Tau is attributed to play a role in the nucleus. Nuclear function of Tau is dependent on its residue-specific phosphorylation. We studied the effect of a green tea polyphenol, EGCG, on the formaldehyde-induced Tau phosphorylation and Tau kinase CDK5. Interestingly, we observed unique localization of phospho-Tau (AT 8 and AT 100) in the nucleus in various EGCG treatments. EGCG was also found to lower the levels of CDK5 in the formaldehyde-treated cells. Further, the role of EGCG was tested in vivo in drosophila eye model of hyperphosphorylated Tau (Tau E14). The results suggest that EGCG can modulate nuclear Tau phosphorylation and lower the levels of Tau kinase CDK5.

cell biology↗

bioRxiv2020

A green tea polyphenol Epigallocatechin-3-gallate modulates Tau Post-translational modifications and cytoskeletal network

BackgroundAlzheimers disease is a type of dementia denoted by progressive neuronal death due to the accumulation of proteinaceous aggregates of Tau. Post-translational modifications like hyperphosphorylation, truncation, glycation, etc. play a pivotal role in Tau pathogenesis. Glycation of Tau aids in paired helical filament formation and abates its microtubule-binding function. The chemical modulators of Tau PTMs, such as kinase inhibitors and antibody-based therapeutics, have been developed, but natural compounds, as modulators of Tau PTMs are not much explored. MethodsWe applied biophysical and biophysical techniques like fluorescence kinetics, SDS-PAGE, western blot analysis and transmission electron microscopy to investigate the impact of EGCG on Tau glycation in vitro. The effect of glycation on cytoskeleton instability and its EGCG-mediated rescue were studied by immunofluorescence in neuroblastoma cells. ResultsEGCG inhibited methyl glyoxal (MG)-induced Tau glycation in vitro. EGCG potently inhibited MG-induced advanced glycation endproducts formation in neuroblastoma cells as well modulated the localization of AT100 phosphorylated Tau in the cells. In addition to preventing the glycation, EGCG enhanced actin-rich neuritic extensions and rescued actin and tubulin cytoskeleton severely disrupted by MG. EGCG maintained the integrity of the Microtubule Organizing Center (MTOC) stabilized microtubules by Microtubule-associated protein RP/EB family member 1 (EB1). ConclusionsWe report EGCG, a green tea polyphenol, as a modulator of in vitro methylglyoxal-induced Tau glycation and its impact on reducing advanced glycation end products in neuroblastoma cells. We unravel unprecedented function of EGCG in remodeling neuronal cytoskeletal integrity.

cell biology↗

bioRxiv2019

Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain

Microtubule-associated protein Tau undergoes aggregation in Alzheimers disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits polyubiquitinated aggregates to the motor protein dynein. Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3{beta} regulation and cytoskeletal organization in neuronal cells by immunocytochemistry. Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre. Our studies suggest the regulatory role of this domain in different aspects of neurodegenerative diseases.

cell biology↗