Molecular Simulation of the Binding of Amyloid Beta to Apolipoprotein A-I in High-Density Lipoproteins.

ABSTRACT: Disrupted clearance of amyloid beta (Aβ) from the brain enhances its aggregation and formation of amyloid plaques in Alzheimer's disease. The most abundant protein constituent of circulating high-density lipoprotein (HDL) particles, apoA-I, readily crosses the blood-brain barrier from periphery circulation, exhibits low-micromolar binding affinity for soluble, neurotoxic forms of Aβ, and modulates Aβ aggregation and toxicity in vitro. Its highly conserved N-terminal sequence, ⁴²LNLKLLD⁴⁸ ('LN'), has been proposed as a binding region for Aβ. However, high-resolution structural characterisation of the mechanism of HDL-Aβ interaction is very difficult to attain. Molecular dynamics simulations were conducted to investigate for the first time the interaction of Aβ and the

SUBMITTER: Malajczuk CJ 

PROVIDER: S-EPMC11818119 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature