Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

Abstract

The onset of amyloidogenic diseases is associated with the misfolding and aggregation of proteins. Despite extensive research, no effective therapeutics are yet available to treat these chronic degenerative diseases. Targeting the aggregation of disease-specific proteins is regarded as a promising new approach to treat these diseases. In the past few years, rapid progress in this field has been made in vitro, in vivo, and in silico to generate potential drug candidates, ranging from small molecules to polymers to nanoparticles. Small molecular probes, mostly those derived from natural sources, have been of particular interest among amyloid inhibitors. Here, we summarize some of the most important natural small molecular probes which can inhibit the aggregation of Aβ, hIAPP, and α-syn peptides and discuss how their binding efficacy and preference for the peptides vary with their structure and conformation. This provides a comprehensive idea of the crucial factors which should be incorporated into the future design of novel drug candidates useful for the treatment of amyloid diseases.

Pathways of hLL-3717-29 Aggregation Give Insight into the Mechanism of α-Amyloid Formation

“…In hll-4, the tetrameric state is the most abundant, almost 12-fold higher than the next most prevalent state [1,3] (Figure 5(a)). We also observed a small but finite probability of the hll-4 systems present as a pair of dimers [2,2]. For hll-8 (Figure 5(b)), state [3,5] is the most abundant, followed by the completely aggregated state [8].…”

“…Amyloids refer to the organized self-assembly of proteins that adopt various structural features ranging from water-soluble aggregates to insoluble plaque-like deposits. 1,2 Depending on the secondary structure of the constituent protein monomer, amyloids can be broadly classified into two categories: α 3,4 and β. 5−8 The domain of β-amyloids has been extensively researched and linked to numerous neurodegenerative and systemic disorders.…”

Exploring the Curvature-Dependence of Boron Nitride Nanoparticles on the Inhibition of hIAPP Aggregation

“…Currently, many clinical trials are being carried out to utilize the above-mentioned inhibitors as drugs against T2D, but the attempts have yet to provide any fruitful results. 68 Hence there is an urgent need to develop an appropriate drug to control this disease. The application of nanoparticles in the modulation of protein aggregation and also in the biomedical field has received significant attention in recent years.…”

“…Currently, many clinical trials are being carried out to utilize the above-mentioned inhibitors as drugs against T2D, but the attempts have yet to provide any fruitful results . Hence there is an urgent need to develop an appropriate drug to control this disease.…”

“…The application of nanoparticles in the modulation of protein aggregation and also in the biomedical field has received significant attention in recent years. In addition, as the research of multitarget amyloid drugs (drugs which can simultaneously target multiple amyloid peptides) is encouraged, many candidates have been identified which can prevent the aggregation of both hIAPP and Aβ. ,,− ,,,− This is further convenient as the sequences of Aβ and hIAPP are not only 50% similar, but are also 25% identical , and, thus, clinical evidence link AD and T2D . Keeping these in mind, the quest to employ nontoxic and biocompatible nanomaterials for the inhibition of hIAPP aggregation led us to speculate the effect of BN nanoparticles on the peptide self-assembly.…”