Isoflurane and desflurane at clinically relevant concentrations induce amyloidbeta-peptide oligomerization: an NMR study

Current understanding on Alzheimer's disease (AD) reveals that soluble amyloid beta-peptide (AP) oligomeric formation plays an important role in AD pathophysiology. A potential role for several inhaled anesthetics in promoting AP oligomer formation has been suggested. Using a nuclear magnetic resonance (NMR) Study, we previously demonstrated that at a high concentration (higher than clinically relevant concentrations), the inhaled anesthetics halothane and isoflurane, interact with specific amino acid residues (G29, A30, and 131) and induce A beta oligomerization. The present study confirms this is true at a clinically relevant concentration. Isoflurane and desflurane induce A beta oligomerization by inducing chemical shift changes of the critical amino acid residues (G29, A30. and 131), reinforcing the evidence that perturbation of these three Crucial residues indeed plays an important role in oligomerization. These findings Support the emerging hypothesis that several commonly used inhaled anesthetics could be involved in neurodegeneration, as well as risk factor for accelerating the onset of AD. (C) 2008 Elsevier Inc. All rights reserved.