Neurodegenerative disorders involve various pathophysiological pathways, and finding a solution for these issues is still an uphill task for the scientific community. In the present study, a combination of molecular docking and dynamics approaches was applied to target different pathways leading to neurodegenerative disorders such as Alzheimer's disease. Initially, abrineurin natural inducers were screened using physicochemical properties and toxicity assessment. Out of five screened compounds, a pentacyclic triterpenoid, i.e., Soyasapogenol B appeared to be the most promising after molecular docking and simulation analysis. Soyasapogenol B showed low TPSA (60.69), high absorption (82.6%), no Lipinski rule violation, and no toxicity. Docking interaction analysis revealed that Soyasapogenol B bound effectively to all of the targeted proteins (AChE, BuChE MAO-A, MAO-B, GSK3β, and NMDA), in contrast to other screened abrineurin natural inducers and inhibitors. Importantly, Soyasapogenol B bound to active site residues of the targeted proteins in a similar pattern to the native ligand inhibitor. Further, 100 ns molecular dynamics simulations analysis showed that Soyasapogenol B formed stable complexes against all of the targeted proteins. RMSD analysis showed that the Soyasapogenol B-protein complex exhibited average RMSD values of 1.94 Å, 2.11 Å, 5.07 Å, 2.56 Å, 3.83 Å and 4.07 Å. Furthermore, the RMSF analysis and secondary structure analysis also indicated the stability of the Soyasapogenol B-protein complexes.
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http://dx.doi.org/10.3390/e24050593 | DOI Listing |
ChemMedChem
December 2024
Central China Normal University, State Key Laboratory of Green Pesticide, CHINA.
Butyrylcholinesterase plays an indispensable role in organisms, and its abnormal expression poses a significant threat to human health and safety, covering various aspects including liver-related diseases, diabetes, obesity, cardiovascular and cerebrovascular diseases, and neurodegenerative diseases. In addition, toxic substances such as organophosphorus and carbamate pesticides markedly inhibit BChE activity. BChE activity serves as a critical parameter for the clinical diagnosis of acute organophosphorus pesticide poisoning and the evaluation of organophosphorus and carbamate pesticide residues.
View Article and Find Full Text PDFMol Cell Biochem
December 2024
Department XIII Infectious Diseases-Parasitology, "Victor Babeș" University of Medicine and Pharmacy of Timișoara, Timișoara, Romania.
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View Article and Find Full Text PDFActa Neuropathol
December 2024
Laboratory for Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute (LBI), KU Leuven (University of Leuven), O&N IV Herestraat 49, Bus 1032, 3000, Leuven, Belgium.
Elife
December 2024
Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
Parkinson's disease (PD) is a multifactorial disease caused by irreversible progressive loss of dopaminergic neurons (DANs). Recent studies have reported the successful conversion of astrocytes into DANs by repressing polypyrimidine tract binding protein 1 (PTBP1), which led to the rescue of motor symptoms in a chemically-induced mouse model of PD. However, follow-up studies have questioned the validity of this astrocyte-to-DAN conversion model.
View Article and Find Full Text PDFUsing a prion amplification assay, we identified prions in tissues from wild pigs (Sus scrofa) living in areas of the United States with variable chronic wasting disease (CWD) epidemiology. Our findings indicate that scavenging swine could play a role in disseminating CWD and could therefore influence its epidemiology, geographic distribution, and interspecies spread.
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