NMR Investigations of Amyloid-beta Peptide Interactions with Propofol at Clinically Relevant Concentrations with and without Aqueous Halothane Solution

Oligomerization of amyloid-beta peptide (A beta) is an important stage in Alzheimer's disease. Recently, it has been shown that in an experimental model, smaller sized anesthetics (e.g., isoflurane, desflurane, etc.) induce A beta oligomerization. Using state-of-the-art solution nuclear magnetic resonance, spectroscopic studies on A beta interaction with propofol indicated that propofol does not interact with the G29, A30, and I31 residues of A beta peptide at a clinically relevant concentration (0.083 mM), and no A beta oligomerization was observed after 69 days. However, A beta oligomerization was observed when treated with propofol (clinically relevant concentration) co-administered with aqueous halothane solution. Furthermore, dose dependence studies at various propofol concentrations (0.32 mM, 2.07 mM, and 53.4 mM) indicate the effect of propofol concentration on A beta oligomerization revealing the hydrophobic nature of interactions between propofol with these critical residues (G29, A30, and I31). These experimental findings reaffirm that smaller molecular sized anesthetics (e.g., halothane) do play a leading role in A beta oligomerization.