# Mechanistic Insights Into Protein Aggregation Inhibition by Green‐Synthesized Silver Nanoparticles: A Study on Human Lysozyme

## TL;DR

This study explores how green-synthesized silver nanoparticles inhibit protein aggregation, a hallmark of diseases like Alzheimer's and Parkinson's.

## Contribution

The paper provides mechanistic insights into the chaperone-like activity of biogenic silver nanoparticles on human lysozyme aggregation.

## Key findings

- Biogenic AgNPs showed concentration-dependent inhibition of human lysozyme aggregation.
- AgNPs exhibited chaperone-like behavior by reducing protein aggregation in astrocytes.
- A range of biophysical techniques confirmed the inhibitory effect of AgNPs on protein aggregation.

## Abstract

A characteristic of many neurodegenerative disorders, such as Parkinson’s and Alzheimer’s, is amyloidogenic protein aggregation, for which there are currently no proven cures. Aging, mutation, and physiological stress can cause proteins to deviate from their natural folding patterns, potentially leading to the formation of hazardous protein aggregates. Noble metal nanoparticles (NPs), due to their unique physicochemical properties, have emerged as promising tools in biomedicine, with applications ranging from tissue engineering to drug delivery and diagnostics. Although concerns regarding cytotoxicity exist, small‐sized silver (Ag) NPs (AgNPs) have demonstrated potential in antiviral, anticancer, and antibacterial therapies. This study investigated the development of biocompatible AgNPs using a green synthesis approach and examined their chaperone‐like activity against protein aggregation, emphasizing the role of meticulous in vitro design. Human lysozyme (HLZ) served as a model protein for aggregation inhibition assays. Biogenic AgNPs exhibited a concentration‐dependent effect on HLZ aggregation, demonstrating an optimal inhibitory concentration, followed by a decrease in efficacy at higher concentrations. Furthermore, astrocytes treated with AgNPs displayed reduced protein aggregation, suggesting a chaperone‐like behavior. The initial phase focused on the detailed characterization of AgNPs synthesized using orange juice extract. Subsequently, this study explored the mechanistic understanding of AgNP‐mediated inhibition of protein aggregation under controlled conditions. A battery of biophysical techniques, including circular dichroism (CD), 8‐anilino‐1‐naphthalene‐sulfonic acid (ANS) fluorescence, thioflavin T (ThT) fluorescence, Congo red (CR) assay, and turbidity measurements, was employed to meticulously assess the inhibitory effect on HLZ aggregation in vitro.