Aβ peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: A NMR study

A beta peptide is the major component of senile plaques (SP) which accumulates in AD (Alzheimer's disease) brain. Reports from different laboratories indicate that anesthetics interact with A beta peptide and induce A beta oligomerization. The molecular mechanism of A beta peptide interactions with these anesthetics was not determined. We report molecular details for the interactions of uniformly (15)N labeled A beta 40 with different anesthetics using 2D nuclear magnetic resonance (NMR) experiments. At high concentrations both isoflurane and propofol perturb critical amino acid residues (G29, A30 and 131) of A beta peptide located in the hinge region leading to A beta oligomerization. In contrast, these three specific residues do not interact with thiopental and subsequently no A beta oligomerization was observed. However, studies with combined anesthetics (thiopental and halothane), showed perturbation of these residues (G29, A30 and 131) and subsequently A beta oligomerization was found. Perturbation of these specific A beta residues (G29, A30 and 131) by different anesthetics could play an important role to induce A beta oligomerization. (C) 2008 Elsevier B.V. All rights reserved.