Active Site Environment and Reactivity of Copper-Aß in Membrane Mimetic SDS Micellar Environment.
Chemistry
; : e202401531, 2024 Jun 20.
Article
em En
| MEDLINE
| ID: mdl-38899478
ABSTRACT
Alzheimer's disease (AD) is characterized by the abnormal aggregation of amyloid ß (Aß) peptide in extracellular deposits generated upon proteolysis of Amyloid Precursor Protein (APP). While copper (Cu(II)) binds to Aß in soluble oligomeric and aggregated forms, its interaction with membrane-bound Aß remains elusive. Investigating these interactions is crucial for understanding AD pathogenesis. Here, utilizing SDS micelles as a simplified membrane mimic, we focus on elucidating the interplay between membrane-anchored Aß and copper, given their pivotal roles in AD. We employed spectroscopic techniques including UV, CD, and EPR to characterize the active site of Cu-Aß complexes. Our findings demonstrate that copper interacts with Aß peptides in membrane-mimicking micellar environments similarly to aqueous buffer solutions. Cu-Aß complexes in this medium also induce higher hydrogen peroxide (H2O2) production, potentially contributing to AD-related oxidative stress. Moreover, we observe an increased oxidation rate of neurotransmitter such as dopamine by Cu-Aß complexes. These results enhance our understanding of Cu-Aß interactions in AD pathology and offer insights into potential therapeutic interventions targeting this interaction.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chemistry
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Índia