Investigating Chaperone like Activity of Green Silver Nanoparticles: Possible Implications in Drug Development.

Mohd Ahmar Rauf,Nemat Ali,Abdullah F Alasmari,Adel Alghamdi,Md Tauqir Alam,Mohd Ishtikhar

doi:10.3390/molecules27030944

Abstract

Protein aggregation and amyloidogenesis have been associated with several neurodegenerative disorders like Alzheimer’s, Parkinson’s etc. Unfortunately, there are still no proper drugs and no effective treatment available. Due to the unique properties of noble metallic nanoparticles, they have been used in diverse fields of biomedicine like drug designing, drug delivery, tumour targeting, bio-sensing, tissue engineering etc. Small-sized silver nanoparticles have been reported to have anti-biotic, anti-cancer and anti-viral activities apart from their cytotoxic effects. The current study was carried out in a carefully designed in-vitro to observe the anti-amyloidogenic and inhibitory effects of biologically synthesized green silver nanoparticles (B-AgNPs) on human serum albumin (HSA) aggregation taken as a model protein. We have used different biophysical assays like thioflavin T (ThT), 8-Anilino-1-naphthalene-sulphonic acid (ANS), Far-UV CD etc. to analyze protein aggregation and aggregation inhibition in vitro. It has been observed that the synthesized fluorescent B-AgNPs showed inhibitory effects on protein aggregation in a concentration-dependent manner reaching a plateau, after which the effect of aggregation inhibition was significantly declined. We also observed meaningful chaperone-like aggregation-inhibition activities of as-synthesized florescent B-AgNPs in astrocytes.

Highlights

Several neurodegenerative chronic disorders like Alzheimer’s, Parkinson’s, systemic amyloidosis, etc., involve the aggregation and deposition of misfolded proteins ranging from small oligomers to large amyloid masses [1,2]
We discovered that biologically synthesized green silver nanoparticles (B-AgNPs) inhibited protein i.e., ver, i.e., 40 °C in vitro. the current study, we discovered that B-AgNPs inhibited protein aggregation a concentration-dependent manner
B-AgNPs may act as a chaperone, preventing protein misfolding in astrocytes

Summary

Introduction

Several neurodegenerative chronic disorders like Alzheimer’s, Parkinson’s, systemic amyloidosis, etc., involve the aggregation and deposition of misfolded proteins ranging from small oligomers to large amyloid masses [1,2]. Amyloids are insoluble proteins characterized by the highly ordered β-sheet rich structural motif [3]. Amyloidosis follows the unfolding mediated misfolding/aggregation of native proteins [4]. Apart from amino acid residues present in the primary polypeptides, other environmental factors may play important roles in gaining functional native structure of proteins [6]. Unfolding-mediated aggregation of native proteins is a critical stage in amyloidosis that is influenced by a variety of environmental factors [7]. Most of the protein aggregates are found to be rich in cross-β sheets which facilitate larger surface area for amyloidosis to take place [8]. Elucidating the insights of protein unfolding mediated aggregation pathways will help in designing better drugs for amyloids related disorders

Methods

Results

Conclusion