Vijay Kumar

Conference 2022 Live Talk

 

Talk title

Inhibitory and disaggregation effect of Ocimum sanctum extract on α-synuclein aggregation

 

Authors and Affiliations

Vijay Kumar1, Vinod Kumar Meena1, Shivani Karalia1

1. National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110 067, India

 

Abstract

Background

α-Synuclein (α-Syn) has a propensity to form amyloids and is one of the major causes of neurodegenerative disorders like Parkinson’s disease (PD). Despite a lot of research, there is no obviating therapy available for PD and related disorders. Therefore, discovering new inhibitors against α-Syn aggregation is a subject of intense research. Against this backdrop, we have investigated the attenuating effect of naturally occurring Ocimum sanctum (OS) against aggregation in aqueous solution using various biochemical and biophysical studies.

Methods

In this report, Thioflavin (ThT) and Congo red binding assays have shown the hindering effect of OS extract on β-sheet formation in α-Syn, . ANS binding assay for effect on hydrophobic patches of α-Syn protein. SDS-PAGE, turbidity measurement, and light scattering assays indicated the role of OS extract in protein solubility. TEM and DLS were used check effect on morphological fibrils . Also, MTT assay implied to understand effect of OS extract on neuroblastoma cells against fibril induced cytotoxicity. Furthermore, docking studies of α-Syn with different molecules of OS extract navigated for putative interacting amino acid residues.

Results

This work suggest OS extract inhibits α-Synuclein aggregation as well as disaggregates pre-existing α-Synuclein fibrils. The polyphenolic compounds present in OS extract binds with α-Syn increase its solubility and inhibits its aggregation. MTT assay confirm OS extract reduces fibril induced toxicity on neuroblastoma( N2a) cells. This work also extends to reveal the inhibitory and disaggregation effects of OS extract on A53T mutant induced aggregation and pre-existing fibrils respectively.

Conclusions

This study implicates that OS extract and associated molecules may become a potential therapeutic intervention against PD and other aggregation related disorders.