Inhibition of fibrillation process and disaggregation of mature fibrils using small peptide are the promising remedial strategies to combat neurodegenerative diseases. However, designing peptide-based drugs to target β-sheet-rich amyloid has been a major challenge. The current work describes, for the first time, the amyloid inhibitory potential of the two short peptides (selected on the basis of predisposition of their amino acid residues toward β-sheet formation) using combination of biophysical, imaging methods, and docking approaches. Results showed that peptides employed different mechanisms to inhibit the amyloid fibrillation. Furthermore, they were also effective in blocking the amyloid fibrillation pathway. In contrary to the insulin fibrillar mesh, significantly less fibrillar species appeared in the presence of peptides, as confirmed by transmission electron microscopy. Circular dichroism analysis indicated that although peptides did not stabilize the native state of insulin, they inhibited amyloid aggregation by reducing the formation of β-sheet rich structures. Hemolytic assay revealed the non-hemolytic nature of the species formed when insulin was co-incubated with the peptides. Therefore, despite the inherent potential to form β-sheet structure, these peptides inhibited the amyloid formation and potentially can be used as therapeutics for the treatment of amyloid-related diseases.
Proteins are central to life functions. Alterations in the structure of proteins are reflected in their function. Misfolded proteins and their aggregates present a significant risk to the cell. Cells have a diverse but integrated network of protection mechanisms. Streams of misfolded proteins that cells are continuously exposed to must be continually monitored by an elaborated network of molecular chaperones and protein degradation factors to control and contain protein misfolding problems. Aggregation inhibition properties of small molecules such as polyphenols are important as they possess other beneficial properties such as antioxidative, anti-inflammatory, and pro-autophagic properties and help neuroprotection. A candidate with such desired features is important for any possible treatment development for protein aggregation diseases. There is a need to study the protein misfolding phenomenon so that we can treat some of the worst kinds of human ailments related to protein misfolding and aggregation.
Globally, people are highly affected by Cadmium (Cd), the most hazardous heavy metal. It has been implicated in various pathogeneses. Oxidative stress may be one the main reasons for Cd-induced disorders in the body. This article investigates the protective ability of Catharanthus roseus (CR) extract on oxidative stress in the kidney and liver of rats exposed to Cd. After 21 days, a significant increase in MDA concentration (6.81 ± 0.05), (6.64 ± 0.03) was observed in Cd-treated groups compared to the control (5.54 ± 0.02), (5.39 ± 0.04) for the kidney and liver, respectively, while significant changes were observed in the haematological parameters. Antioxidant enzymes, GPx, CAT, and SOD showed a significant decrease in their activity. We established that increasing the concentration of Cd in the presence of H2O2 was able to cause stand scission in pBR322 plasmid DNA, which may be due to the mediation of ROS generated in the process. The antioxidant ability of CR extract was tested in DPPH and H2O2 scavenging assay, depicted by the increase in the percentage inhibition. Upon treatment of CR extract to rats, MDA concentration was decreased for the kidney and liver compared to the Cd-treated groups. This was again confirmed by comet assay of both tissues, where the degree of cellular DNA breakage caused by Cd toxicity decreased significantly upon treatment with CR extract. Overall, the results suggest that Cd plays a major role as an effector metal ion, causing a decrease in the concentration and activity of AO enzymes and enhanced lipid peroxidation. ROS production resulted in oxidative DNA damage within the cell, whereas CR extract showed potential antioxidant activity against ROS-mediated DNA damage induced by Cd poisoning.
The root-knot nematode Meloidogyne incognita is one of the most damaging plant-parasitic nematodes and is responsible for significant crop losses worldwide. Rising human health and environmental concerns have led to the withdrawal of commonly used chemical nematicides. There has been a tremendous demand for eco-friendly bio-nematicides with beneficial properties to the nematode hosting plants, which encourages the need for alternative nematode management practices. The current study was undertaken to determine the nematicidal potential of cotton seed cake (CSC) against second-stage juvenile (J2) hatching, J2 mortality, and J2 penetration of M. incognita in tomato plants in vitro. J2s and egg masses of M. incognita were exposed to four concentrations (250, 500, 750, and 1000 mg/L) of CSC extracts. The higher J2 mortality and inhibition of J2 hatching were found at 1000 mg/L, while the least effective result was observed at 250 mg/L of the CSC extract. The CSC extract applied with the concentrations mentioned above also showed inhibition of J2 penetration in tomato roots; 1000 mg/L showed the highest inhibition of penetration, while 250 mg/L displayed the least inhibition. Using gas chromatography-mass spectroscopy, we identified 11 compounds, out of which 9,12-Octadecadienoic acid, Hexadecanoic acid, and Tetradecanoic acid were found as major compounds. Subsequently, in silico molecular docking was conducted to confirm the nematicidal behavior of CSC based on binding interactions of the above three major compounds with the targeted protein acetylcholine esterase (AChE) of M. incognita. The values of binding free energy are −5.3, −4.5, and −4.9 kcal/mol, observed for 9,12-Octadecadienoic acid, n-Hexadecanoic acid, and Tetradecanoic acid, respectively, suggesting that 9,12-Octadecadienoic acid binds with the receptor AChE more efficiently than the other two ligands. This study indicates that CSC has nematicidal potential that can be used to control M. incognita for sustainable agriculture.
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