Chaperone Like Attributes of Biogenic Fluorescent Gold Nanoparticles: Potential to Alleviate Toxicity Induced by Intermediate State Fibrils Against Neuroblastoma Cells.

Anzar Abdul Mujeeb,Irfan Ahmad Ghazi,Fauzia Jamal,Mohd Kashif,Khan Farheen Badre Alam,Mohammad Owais,Anees Ahmed,Ansam Wadia Faid Alshameri,Saba Farheen

doi:10.3389/fchem.2019.00787

Abstract

In general, neurodegenerative disorders have a great deal of correlation with the misfolded as well as aggregated forms of protein-based macromolecules. Among various species formed during the aggregation process, protein oligomers have been classified as most toxic entities against several types of living cells. A series of chemicals have been developed to inhibit protein aggregation as a measure to regulate neurodegenerative diseases. Recently, various classes of nanoparticles have also been reported to inhibit protein aggregation. In the present study, we synthesized fluorescent gold nanoparticles (B-AuNPs) employing Olax scandens leaf extract. Next, an in vitro study was performed to assess the effect of as-synthesized B-AuNPs on the aggregation behavior of the ovalbumin (OVA) and other related model proteins. We performed an extensive study to elucidate anti-amyloidogenic properties of nano-sized entities and established that small-sized B-AuNPs manifest chaperone potential against protein aggregation. Further, we exploited as-synthesized B-AuNPs as a mean to prevent protein aggregation mediated toxicity in neuroblastoma cells.

Highlights

Amyloidal protein toxicity has a strong implication in several neurodegenerative disorders such as Alzheimer’s, Parkinson’s (PD), Huntington’s, and Prion disease, etc. (Chung et al, 2018)
The incubation with increasing concentration of Olax extract resulted in an increase in the magnitude of absorbance with characteristic surface plasmon resonance peaks of gold nanoparticles in the range of 510– 540 nm
To establish that B-AuNPs mediated inhibition of fibril formation is a universal phenomenon, we extended this inhibition study with another model protein human serum albumin (HSA)

Summary

INTRODUCTION

Amyloidal protein toxicity has a strong implication in several neurodegenerative disorders such as Alzheimer’s, Parkinson’s (PD), Huntington’s, and Prion disease, etc. (Chung et al, 2018). An attractive alternative approach to regulate protein aggregation process is to use artificial chaperone, in the form of nanoparticles, to inhibit the synthesis of amyloidogenic fibril structures (Young et al, 2017). We studied the effect of as-synthesized B-AuNPs on the generation of aggregate associated toxic species and their potential to inhibit neuroblastoma (SH-SY5Y) cells. Fluorescence Imaging to Study the Toxic Effect of Fibril (Formed in the Presence of As-Synthesized B-AuNPs) on Human Neuroblastoma Cells The human neuroblastoma cell line (SH-SY5Y) cells were cultured overnight in the CO2 incubator (5% CO2, 37◦C). The log phase cells were incubated with fibril formed in the presence of increasing concentration of as-synthesized B-AuNPs. MTT Cell Viability Assay The toxicity of OVA fibril on SH-SY5Y neuroblastoma cells was determined by employing MTT assay.

RESULTS

DISCUSSION

DATA AVAILABILITY STATEMENT