Carboxylic Group Functionalized Carbon Quantum Dots inhibit Hen Egg White Lysozyme Amyloidogenesis, leading to the Formation of Spherical Aggregates with Reduced Toxicity and ROS Generation.

INTRODUCTION: Proteinopathies are a group of diseases where the protein structure has been altered. These alterations are linked to the production of amyloids, which are persistent, organized clumps of protein molecules through inter-molecular interactions. Several disorders, including Alzheimer's and Parkinson's, have been related to the presence of amyloids. Highly ordered beta sheets or beta folds are characteristic of amyloids; these structures can further self- -assemble into stable fibrils. METHOD: Protein aggregation is caused by a wide variety of environmental and experimental factors, including mutations, high pH, high temperature, and chemical modification. Despite several efforts, a cure for amyloidosis has yet to be found. Due to its advantageous semi-conducting characteristics, unique optical features, high surface area-to-volume ratio, biocompatibility, etc., carbon quantum dots (CQDs) have lately emerged as key instruments for a wide range of biomedical applications. To this end, we have investigated the effect of CQDs with a carboxyl group on their surface (CQD-CA) on the in vitro amyloidogenesis of hen egg white lysozyme (HEWL). RESULT: By generating a stable compound that is resistant to fibrillation, our findings show that CQD-CA can suppress amyloid and disaggregate HEWL. In addition, CQD-CA caused the creation of non-toxic spherical aggregates, which generated much less reactive oxygen species (ROS). CONCLUSION: Overall, our results show that more research into amyloidosis treatments, including surface functionalized CQDs, is warranted.

Amine Group Surface-Functionalized Carbon Quantum Dots Exhibit Anti-amyloidogenic Effects Towards Hen Egg White Lysozyme by Inducing Formation of Nontoxic Spherical Aggregates.

The tendency of polypeptide chains to deviate from their conventional protein folding pathway and instead get trapped as off-pathway intermediates, has been a matter of great concern. These off-pathway intermediates eventually lead to the formation of insoluble, ordered fibrillar aggregates called amyloids, which are responsible for a host of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and Type II diabetes. In spite of extensive research, development of an effective therapeutic strategy against amyloidosis still remains elusive. In recent times, carbon quantum dots (CQD) have grabbed the attention of researchers against amyloidogenesis due to their ease of preparation, aqueous soluble nature, unique optical properties, high surface to volume ratio, physio-chemical properties, semi-conducting nature and mainly biocompatible. In the current study, we have reported an easy-to-prepare procedure for synthesis of amine group surface functionalized CQDs from commonly available kitchen spices with anti-oxidant properties. The as-synthesized CQDs were evaluated for their anti-amyloidogenic properties towards Hen Egg White Lysozyme (HEWL). Our results clearly show that the surfaced functionalized CQDs were able to interact with HEWL, thereby forming a stable complex, which was resistant towards amyloid formation and instead lead to the formation of non-toxic globular aggregates.

Inhibitory effects of carbon quantum dots towards hen egg white lysozyme amyloidogenesis through formation of a stable protein complex.

Proteins, under certain circumstances such as defective quality control mechanism, mutations and altered environmental conditions, undergo misfolding and assemble into highly ordered beta-sheet structured fibrillar aggregates called amyloid fibrils. Formation of amyloid is seen in most of the protein linked degenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, Type II diabetes mellitus and many more. Amyloid fibril forms via intermediate state(s), and is known to follow a nucleated condensation polymerization mechanism. Though extensive research is being carried out towards finding a therapeutic solution to the amyloidosis, an effective treatment to these diseases still remains elusive and also the mechanism of amyloidogenesis largely remains unclear. In recent times, carbon quantum dots (CQDs) are gaining the attention of researchers due to their semi-conductive nature, excellent physio-chemical properties, high surface to volume ratio, optical properties and mainly bio-compatibility. In the current study, we have synthesized CQDs from commonly available kitchen spice mix and explored their role in amyloidogenesis using hen egg white lysozyme (HEWL) as a model protein. The results clearly demonstrate the amyloid inhibitory as well as disaggregation potential of CQD by forming a stable complex with HEWL and thereby increasing the energy barrier for the aggregation process.

Quantum Dots as Promising Theranostic Tools Against Amyloidosis: A Review.

Amyloids are highly ordered beta sheet rich stable protein aggregates, which have been found to play a significant role in the onset of several degenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's disease, Type II diabetes mellitus and so on. Aggregation of proteins leading to amyloid fibril formation via intermediate(s), is thought to be a nucleated condensation polymerization process associated with many pathological conditions. There has been extensive research to identify inhibitors of these disease oriented aggregation processes. In recent times, quantum dots, with their unique physico-chemical properties have grabbed the attention of scientific community due to its applications in medical sciences. Quantum dots are nano-particles usually made of semiconductor materials which emit fluorescence upon radiation. The wavelength of fluorescence emission varies with changes in size of quantum dots. Several studies have reported significant inhibitory effects of these quantum dots towards amyloidogenesis, thereby presenting themselves as promising candidates against amyloidosis. Further, studies have also revealed amyloid detection capacity of quantum dots with sensitivity and specificity better than conventional probes. In the current review, we will discuss the various effects of quantum dots on protein aggregation pathways, their mechanism of actions and their potentials as effective therapeutics against amyloidosis.