title: NMR investigations of amyloid-β peptide interactions with propofol at clinically relevant concentrations with and without aqueous halothane solution.
abstract: Oligomerization of amyloid-β peptide (Aβ) 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 Aβ oligomerization. Using state-of-the-art solution nuclear magnetic resonance, spectroscopic studies on Aβ interaction with propofol indicated that propofol does not interact with the G29, A30, and I31 residues of Aβ peptide at a clinically relevant concentration (0.083 mM), and no Aβ oligomerization was observed after 69 days. However, Aβ oligomerization was observed when treated with propofol (clinically relevant concentration) coadministered 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 Aβ 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 Aβ oligomerization.
authors.affiliation: Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Center, Manesar, Gurgaon, India. pravat.mandal@gmail.com
authors.forename: Pravat K
authors.initials: PK
authors.lastname: Mandal
authors.forename: Neel S
authors.initials: NS
authors.lastname: Bhavesh
authors.forename: Virender S
authors.initials: VS
authors.lastname: Chauhan
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fodale
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards*; D008956:Models, Chemical; D015742:Propofol / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding / Q000502:physiology; D012996:Solutions / Q000032:analysis / Q000378:metabolism*; D014867:Water / Q000032:analysis / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D012996:Solutions; D014867:Water; D006221:Halothane; D015742:Propofol