Affiliations: Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Centre, Manesar, Gurgaon, India | [x] Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Center, Manesar, Gurgaon, India | [y] Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Policlinico G. Martino, Messina, Italy
Correspondence:
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Correspondence to: Dr. Pravat K. Mandal, Additional Professor (Scientist V), Neurospectroscopy and Neuroimaging Laboratory. E-mail: pravat.mandal@gmail.com.
Abstract: Laboratory research on anesthetic-induced structural changes of amyloid beta (Aβ) peptide, from normal monomeric α-helix to the micro-aggregated form, has generated much interest in the scientific community as Aβ oligomerization is considered a key step in Alzheimer disease pathogenesis. A comprehensive review of the interactions of Aβ peptide with anesthetics of different molecular sizes is summarized as follows. Smaller sized anesthetics could access and perturb the cavity containing crucial amino acid residues G29, A30 and I31 of Aβ peptide leading to Aβ oligomerization. However, bulkier sized anesthetics are sterically hindered from accessing the cavity containing these crucial residues and do not initiate Aβ oligomerization. Notably, when a small sized anesthetic is co-administered with a larger sized one, the latter does not prevent access of the small sized anesthetic to the cavity. The results of these biophysical studies are supported by animal model studies which indicate that inhaled small molecular anesthetics induce enhanced Aβ plaque deposition in transgenic mice with AD pathology. In this review, a molecular pathway for the A$\beta $-anesthetic interaction at the atomic level is presented.
