Modulation of beta-amyloid aggregation using ascorbic acid.

Autor: Sampaio I; GNano - Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil., Quatroni FD; GNano - Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil., Pincela Lins PM; GNano - Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil., Nascimento AS; Molecular Biotechnology Group, Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil., Zucolotto V; GNano - Nanomedicine and Nanotoxicology Group, Physics Institute of São Carlos, University of São Paulo, CP 369, 13560-970, São Carlos, SP, Brazil. Electronic address: zuco@ifsc.usp.br.
Jazyk: angličtina
Zdroj: Biochimie [Biochimie] 2022 Sep; Vol. 200, pp. 36-43. Date of Electronic Publication: 2022 May 16.
DOI: 10.1016/j.biochi.2022.05.006
Abstrakt: Studies have shown that the level of ascorbic acid (AA) is reduced in the brain of Alzheimer's disease (AD) patients. However, its effect on amyloid-β 1-42 (Aβ 42 ) aggregation has not yet been elucidated. Here we investigated for the first time the effect of AA on Aβ 42 aggregation using fluorescence assay, circular dichroism, atomic force microscopy, isothermal titration calorimetry, ligand docking, and molecular dynamics. Our results showed that the fibril content decreases in the growth phase when the peptides are co-incubated with AA. AA molecules bind to Aβ 42 peptides with high binding affinity and a binding site for AA between the β-strands of Aβ 42 oligomers prevents the stack of adjacent strands. We demonstrate the inhibitory effect of AA on the aggregation of Aβ 42 and its molecular interactions, which can contribute to the development of an accessible therapy for AD and also to the design of novel drugs for other amyloidogenic diseases.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022. Published by Elsevier B.V.)
Databáze: MEDLINE
Externí odkaz: