From Small Molecules to Synthesized Polymers: Potential Role in Combating Amyloidogenic Disorders

Abstract

The concept of developing novel anti-amyloid inhibitors in the scientific community has engrossed remarkable research interests and embraced significant potential to resolve numerous pathological conditions including neurological as well as non-neuropathic disorders associated with amyloid protein aggregation. These pathological conditions have harmful effects on cellular activities which include malfunctioning of organs and tissue, cellular impairment, etc. To date, different types of small molecular probes like polyphenolic compounds, nanomaterials, surfactants, etc. have been developed to address these issues. Recently synthetic polymeric materials are extensively investigated to explore their role in the protein aggregation pathway. On the basis of these perspectives, in this review article, we have comprehensively summarized the current perspectives on protein misfolding and aggregation and importance of therapeutic approaches in designing novel effective inhibitors. The main purpose of this review article is to provide a detailed perspective of the current landscape as well as trailblazing voyage of various inhibitors ranging from small molecular probes to polymeric scaffolds in the field of protein misfolding and aggregation. A particular emphasis is given on the structural role and molecular mechanistic pathway involved in modulating the aggregation pathway to further inspire the researchers and shed light in this bright research field.

Modulating Insulin Aggregation with Charge Variable Cholic Acid-Derived Polymers

“…Substantial research efforts were devoted in the past few years to develop novel anti-amyloidogenic agents to reduce the insulin amyloid fibrillation process. , Numerous potential agents were discovered to arrest the formation of amyloid fibrils , and diminish the amyloid-induced cytotoxicity both in vitro and in vivo , which include flavonoids, surfactants, vitamins, peptides, nanoparticles, various types of drugs, etc. Apart from small molecules, recently, polymers have gained significant attention in preventing the amyloid protein aggregation pathway owing to their unique physio-chemical properties. , Mounting evidence addressed the fact that polymers and polymeric nanomaterials are much more superior compared to small molecule inhibitors owing to their surface modification ability, biocompatibility, probability of forming various architectures, well-controlled degradation rate, and excellent in vivo stability.…”

“…Substantial research efforts were devoted in the past few years to develop novel anti-amyloidogenic agents to reduce the insulin amyloid fibrillation process. 7,8 Numerous potential agents were discovered to arrest the formation of amyloid fibrils 9,10 and diminish the amyloid-induced cytotoxicity both in vitro and in vivo, which include flavonoids, 11 surfactants, 12 vitamins, 13 peptides, 14 nanoparticles, 15 various types of drugs, 16 etc. Apart from small molecules, recently, polymers have gained significant attention in preventing the amyloid protein aggregation pathway owing to their unique physiochemical properties.…”

Mechanistic Insight into the Design of Chemical Tools to Control Multiple Pathogenic Features in Alzheimer’s Disease

“…The molecules in Class III exhibited inhibitory reactivity against AChE through disrupting substrate binding at the active site. In addition to these small molecules, chemical tools composed of nanoparticles, polymers, metal complexes, and peptides have also been developed. − In vivo efficacies of small molecules toward cognitive defects found in AD transgenic mouse models could further highlight the necessity of developing chemical tools with multiple reactivities to advance our understanding of the intertwined roles of pathogenic factors in the pathology of AD. − , …”

Side‐chain amino‐acid‐based polymers: self‐assembly and bioapplications

“…101 Considering the fascinating features of selfassembled amino-acid-based polymeric nanostructures, numerous research groups have focused on applying these materials in the protein aggregation field. 102,103 In this regard, Debnath et al have fabricated biopolymeric micelles that contained a polyaspartic acid backbone along with oleyl amine, ethylenediamine and arginine functional groups; the synthesized biopolymeric micelles clear the amyloid aggregated species from the cells through an upregulated cellular autophagy process. 104 The surface properties and the balanced chemical composition of the biopolymeric micelles play crucial roles and facilitate the upregulated autophagy process for completely clearing the amyloid aggregates from the cell.…”