Molecular Integrative Study on Inhibitory Effects of Pentapeptides on Polymerization and Cell Toxicity of Amyloid-ß Peptide (1-42).
Curr Issues Mol Biol
; 46(9): 10160-10179, 2024 Sep 14.
Article
em En
| MEDLINE
| ID: mdl-39329958
ABSTRACT
Alzheimer's Disease (AD) is a multifaceted neurodegenerative disease predominantly defined by the extracellular accumulation of amyloid-ß (Aß) peptide. In light of this, in the past decade, several clinical approaches have been used aiming at developing peptides for therapeutic use in AD. The use of cationic arginine-rich peptides (CARPs) in targeting protein aggregations has been on the rise. Also, the process of peptide development employing computational approaches has attracted a lot of attention recently. Using a structure database containing pentapeptides made from 20 L-α amino acids, we employed molecular docking to sort pentapeptides that can bind to Aß42, then performed molecular dynamics (MD) analyses, including analysis of the binding stability, interaction energy, and binding free energy to screen ligands. Transmission electron microscopy (TEM), circular dichroism (CD), thioflavin T (ThT) fluorescence detection of Aß42 polymerization, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay, and the flow cytometry of reactive oxygen species (ROS) were carried out to evaluate the influence of pentapeptides on the aggregation and cell toxicity of Aß42. Two pentapeptides (TRRRR and ARRGR) were found to have strong effects on inhibiting the aggregation of Aß42 and reducing the toxicity of Aß42 secreted by SH-SY5Y cells, including cell death, reactive oxygen species (ROS) production, and apoptosis.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China