Dual regulatory effects of neferine on amyloid-ß and tau aggregation studied by in silico, in vitro, and lab-on-a-chip technology.
Biomed Pharmacother
; 172: 116226, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38301421
ABSTRACT
Alzheimer's disease (AD) is characterized by the presence of two critical pathogenic factors amyloid-ß (Aß) and tau. Aß 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 Aß 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 Aß or tau aggregation/dissociation. Herein, we investigated the dual regulatory effects of neferine on Aß and tau aggregation/dissociation. We predicted the binding characteristics of neferine to Aß 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 Aß42 and tau K18. We verified the effect of neferine on Aß fibril degradation using a microfluidic device. In addition, molecular dynamics simulation was used to predict a conformational change in the Aß42-neferine complex. Moreover, we examined the neuroprotective effect of neferine against neurotoxicity induced by Aß 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 Aß and tau pathology.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndromes Neurotóxicas
/
Benzilisoquinolinas
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article