Future Direction of Designing Antioxidant Polymers in Modulating Protein Aggregation Process

Abstract

Amyloids are highly ordered aggregates of misfolded proteins, related to a large number of neurodegenerative diseases including Alzheimer’s, Parkinson’s, type II diabetes and many other debilitating disorders. The misfolded proteins are most commonly [Formula: see text]-sheet rich fibrillar aggregates, and one of the most common therapeutic approaches for the treatment of these disorders is inhibiting the formation of fibrillar aggregates. To date, a myriad of compounds have been introduced for this purpose, however poor water solubility and low bioavailability are major restrictions to achieve this purpose. To overcome these limitations, polymeric materials could be a great choice because of their many unique properties. Furthermore, oxidative stress is a key factor associated with the aforementioned disorders. In this context, natural polyphenolic compounds are attracting attention due to their abundance, potential antioxidant activities and nontoxic nature. Considering the importance of antioxidant agents in preventing the protein aggregation process, the design of novel antioxidant polymers has become a challenging task nowadays. Based on these perspectives, this review aims to provide an overall idea about the protein misfolding process, mechanistic pathway, and therapeutic approaches. The main focus of this review is the use of antioxidant molecules and the integration of natural polyphenol-based antioxidants with polymers for designing next-generation potential anti-amyloidogenic agents.

Insulin fibril inhibition using glycopolymeric nanoassemblies

“…have been reported as potential anti-amyloidogenic agents. 18,19 Apart from natural and synthesized small molecules, various polymeric compounds 20 have been found to prevent protein aggregation, such as polymer nanoparticles, 21 star polymers, 22 dendrimers, 23 amino acid-based polymeric peptides, 24 zwitterionic polymers, 25 glycopolymers, 26,27 etc. Glycopolymers or synthetic polymers with pendant carbohydrate groups have gained massive attention for their potential in biomedical applications because glycopolymers promote biocompatibility to various materials.…”

Antioxidant Polymers with Enhanced Neuroprotection Against Insulin Fibrillation

“…[12,13] A plethora of antioxidant compounds have been reported to diminish the oxidative stress induced by amyloid aggregated species. [14,15] However, their efficacy is often criticized because of the high instability, low bioavailability, and faster clearance rate from the body, which really exerts a therapeutic effect. [16] Vitamin-based antioxidants are degraded once ingested or do not reach the desired targeted site because of unfavorable biodistribution or absorption limits.…”

Amino Acid-Based Polymer-Coated Silver Nanoparticles as Insulin Fibril Inhibitors

“…As a preventive measure, various types of therapeutic agents such as surfactants, chemical osmolytes, chaperones, polyphenols, small peptides, nanoparticles (NPs), antioxidant polymers, polymeric micelles, , several drugs, enzyme inhibitors, and gene therapy method have been reported to prevent the formation of amyloid aggregates. Even though a large number of antiamyloidogenic agents have been designed for averting the protein fibrillation pathway, the major concern in these current remedies is the lower stability of the compounds in the biological system and the poor permeability through the blood–brain barrier (BBB).…”

“…Furthermore, formation of insulin fibrils is a foremost concern during the manufacture of insulin, for long-term storing purposes, and for long-distance shipping of the protein, and any degree of formation of amyloid aggregations results in a reduced efficacy of insulin administration. 5 As a preventive measure, various types of therapeutic agents such as surfactants, chemical osmolytes, 6 chaperones, 7 polyphenols, 8 small peptides, 9 nanoparticles (NPs), 10 antioxidant polymers, 11 polymeric micelles, 12,13 several drugs, 14 enzyme inhibitors, 15 and gene therapy method 16 have been reported to prevent the formation of amyloid aggregates. Even though a large number of antiamyloidogenic agents have been designed for averting the protein fibrillation pathway, the major concern in these current remedies is the lower stability of the compounds in the biological system and the poor permeability through the blood−brain barrier (BBB).…”