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.
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.
The bark extract of Mimusops elengi is rich in different types of plant secondary metabolites such as flavonoids, tannins, triterpenoids and saponins. The present study shows the usefulness of the bark extract of Mimusops elengi for the green synthesis of gold nanoparticles in water at room temperature under very mild conditions. The synthesis of the gold nanoparticles was complete within a few minutes without any extra stabilizing or capping agents and the polyphenols present in the bark extract acted as both reducing as well as stabilizing agents. The synthesized colloidal gold nanoparticles were characterized by HRTEM, surface plasmon resonance spectroscopy and X-ray diffraction studies. The synthesized gold nanoparticles have been used as an efficient catalyst for the reduction of 3-nitrophenol and 4-nitrophenol to their corresponding aminophenols in water at room temperature.
Insulin fibril formation is considered as the hallmark of several debilitating pathological conditions. To develop effective therapeutics that are able to control the amyloidogenesis process and inhibit fibril formation, herein we have designed a side-chain proline (Pro)-based homopolymer and block copolymers through the reversible addition−fragmentation chain transfer (RAFT) polymerization technique and further explored their obligatory role in the in vitro insulin fibrillation process. Using a variety of biophysical tools, including turbidity measurements, thioflavin T (ThT) fluorescence kinetics, tyrosine (Tyr) fluorescence study, Nile red (NR) fluorescence assay, dynamic light scattering (DLS) study, circular dichroism (CD) measurements, and isothermal titration calorimetry (ITC) techniques, we demonstrated that Pro-based polymers can significantly inhibit the insulin fibrillation process. Among them, the Pro-based homopolymer acts as the most potent inhibitor of insulin fibrillation as confirmed by ThT assay, CD study, and transmission electron microscopic (TEM) analysis. Tyrosine fluorescence measurements and NR fluorescence assay revealed that hydrophobic interactions are the crucial factor that mainly controls the inhibition process. Apart from hydrophobic interactions, polar interactions may also be responsible for the inhibition process as evaluated by ITC study.
The design and development of side-chain amino-acid-based polymeric nanostructures have attracted a significant research interest as they bring a remarkable revolution in various territories of the biomedical field. The incorporation of amino acid moieties into the side chain of synthetic polymeric scaffolds exhibits several beneficial properties like aqueous solubility, chiral recognition, high biocompatibility, stimuli responsiveness, antifouling properties, as well as their capability to form higher ordered self-assembled architectures. Considering the important features and widespread applications of side-chain aminoacid-containing polymers, here we shed light on the self-assembled characteristics of side-chain amino-acid-containing polymers and their implications. The primary aim of this review article is to highlight the recent achievements of this bright area of research. We describe the numerous aspects of side-chain amino-acid-containing polymers focusing mainly on self-assembly properties and the biomedical applications, which include drug and gene delivery, antimicrobial activity, antifouling coating, wound healing, tissue engineering etc.
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