Dual regulatory effects of neferine on amyloid-β and tau aggregation studied by in silico, in vitro, and lab-on-a-chip technology - 29/02/24
Abstract |
Alzheimer’s disease (AD) is characterized by the presence of two critical pathogenic factors: amyloid-β (Aβ) and tau. Aβ and tau become neurotoxic aggregates via self-assembly, and these aggregates contribute to the pathogenesis of AD. Therefore, there has been growing interest in therapeutic strategies that simultaneously target Aβ and tau aggregates. Although neferine has attracted attention as a suitable candidate agent for alleviating AD pathology, there has been no study investigating whether neferine affects the modulation of Aβ or tau aggregation/dissociation. Herein, we investigated the dual regulatory effects of neferine on Aβ and tau aggregation/dissociation. We predicted the binding characteristics of neferine to Aβ and tau using molecular docking simulations. Next, thioflavin T and atomic force microscope analyses were used to evaluate the effects of neferine on the aggregation or dissociation of Aβ42 and tau K18. We verified the effect of neferine on Aβ fibril degradation using a microfluidic device. In addition, molecular dynamics simulation was used to predict a conformational change in the Aβ42-neferine complex. Moreover, we examined the neuroprotective effect of neferine against neurotoxicity induced by Aβ and tau and their fibrils in HT22 cells. Finally, we foresaw the pharmacokinetic properties of neferine. These results demonstrated that neferine, which has attracted attention as a potential treatment for AD, can directly affect Aβ and tau pathology.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Neferine inhibits aggregation of Aβ and tau. |
• | Neferine promotes the degradation of Aβ and tau fibrils. |
• | Neferine disassembles Aβ fibrils in microfluidic chips. |
• | Neferine protects against Aβ/tau-induced neurotoxicity in HT22 hippocampal cells. |
• | Neferine exerts dual modulatory activity on Aβ and tau pathology. |
Keywords : Amyloid β, Tau, Neferine
Plan
Vol 172
Article 116226- mars 2024 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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