Modulation of Amyloid Protein Fibrillation by Synthetic Polymers: Recent Advances in the Context of Neurodegenerative Diseases

Abstract

Protein misfolding and aggregation have attracted immense research interests due to their connection with an array of degenerative diseases including neurodegenerative disorders and non-neuropathic diseases. Inhibition or diminution of the formation of protein aggregates is considered as a potential therapeutic strategy to cure these debilitating maladies. A large number of compounds including flavonoids, surfactants, osmolytes, vitamins, nanoparticles, etc. have been explored for impeding protein aggregation process and ameliorating neurodegenerative disorders. Even though a plethora of strategies have been designed to suppress protein aggregation, the final success rate is limited due to the lack of in-depth understanding of the aggregation pathway. In this context, polymeric materials are attracting the attention of researchers owing to their multifarious applications in the field of biomedical science and technology, and their unique properties as many parameters like functionality, molecular weight, architecture, etc. can be easily manipulated to improve their efficacy as well as meet clinical requirements. This review article highlights an outline of protein misfolding and aggregation, their mechanistic pathway, the factors responsible for aggregation, and potential therapeutic strategies for the intervention of those debilitating pathological conditions. Especially, the primary focus of this review article is to delineate the obligatory role of polymeric materials on protein aggregation pathway and encourage researchers to fabricate effective polymeric materials for designing next generation antiamyloidogenic therapeutic agents.

Antimicrobial α-defensins as multi-target inhibitors against amyloid formation and microbial infection

“…Specifically, current prevailing "amyloid cascade hypothesis" strongly believes that the misfolding and aggregation of intrinsically disordered proteins into highly ordered, β-structure-rich species (namely amyloids) is mainly responsible for a central pathogenic cause of PMDs [4][5][6] , e.g., the abnormal aggregation of Aβ, hIAPP, α-synuclein and hCT is associated with AD, T2D, PD, and MTC, respectively. Significant efforts and progresses have been made to develop different types of amyloid inhibitors (i.e., small organic molecules 7,8 , nanoparticles 9 , antibodies 10,11 , polymers 12 , and peptides 13,14 ) to prevent the production and aggregation of amyloid proteins. However, these inhibitors are mostly limited to single-target prevention strategies against specific amyloid proteins/aggregates, leading to no success for clinical cures of PMDs.…”

Styrene‐Maleimide/Maleic Anhydride Alternating Copolymers: Recent Advances and Future Perspectives

“…The auto‐fluorescent behavior will not only help to locate the polymer in bioimaging or drug delivery applications but also prevent unwanted hazards generated from the usage of the conventional fluorophores. [ 135 ] Also, we strongly believe that the advantages of using S‐MI/MA alternating copolymer polymeric skeleton can be further extended to other fields of research like fibril inhibition in various proteins, [ 136 ] as antifouling polymer for biomedical applications, and developing novel adhesive materials. Nevertheless, this review will provide the researchers a detailed discussion on the synthesis of the S‐MI/MA alternating copolymers, the scope of functionalization on the polymeric backbone, and the future prospects.…”

Discotic material hexakis(4‐carboxyphenylethynyl)benzene inhibits Escherichia coli growth via the glycolysis pathway

“…Even when cell entry is permitted, synthetic chemicals normally have a small volume, and therefore a short retention period in the body after their uptake 9 . These small chemicals have recently been embedded in polymers, 10 liposomes, 2 or nanoparticles 11 to increase the efficiency of their transportation and to improve their retention times 12 . Discotic materials with planar and nanoparticle functions 13,14 are potential carriers of these chemicals and should increase their bioavailability; therefore, we investigated their toxicity based on their inhibition of Escherichia coli growth as well as a simple proteomic analysis.…”