Molecular Insights for Alzheimer's Disease: An Unexplored Storyline on the Nanoscale Impact of Nascent Aß1-42 toward the Lipid Membrane.
ACS Appl Mater Interfaces
; 15(14): 17507-17517, 2023 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-36995989
ABSTRACT
Deciphering the mechanism of Alzheimer's disease is a key element for designing an efficient therapeutic strategy. Molecular dynamics (MD) calculations, atomic force microscopy, and infrared spectroscopy were combined to investigate ß-amyloid (Aß1-42) peptide interactions with supported lipid bilayers (SLBs). The MD simulations showed that nascent Aß1-42 monomers remain anchored within a model phospholipid bilayer's hydrophobic core, which suggests their stability in their native environment. We tested this prediction experimentally by studying the behavior of Aß1-42 monomers and oligomers when interacting with SLBs. When Aß1-42 monomers and oligomers were self-assembled with a lipid bilayer and deposited as an SLB, they remain within the bilayers. Their presence in the bilayers induces destabilization of the model membranes. No specific interactions between Aß1-42 and the SLBs were detected when SLBs free of Aß1-42 were exposed to Aß1-42. This study suggests that Aß can remain in the membrane after cleavage by γ-secretase and cause severe damage to the membrane.
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MEDLINE
Assunto principal:
Doença de Alzheimer
Idioma:
En
Ano de publicação:
2023
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Article