Alzheimer’s Disease: Halothane Induces Aβ Peptide to Oligomeric Form—Solution NMR Studies

Abstract

Alzheimer's disease (AD) is a significant contributor to cognitive decline and is responsible for about half of the cases of dementia in later life. Although exact etiology of AD is not known, however, many risk factors for AD are identified. Anesthesia for elderly patients is considered as a risk factor in AD as they frequently experience deterioration in cognitive function with long exposure to anesthetics during surgery. Inhaled anesthetic agents remain the mainstay for patients undergoing major surgical operations. This study using multidimensional NMR spectroscopy provides the first direct evidence in vitro that inhaled anesthetic, halothane specifically interacts with Abeta40 and Abeta42 peptide. Halothane induces structural alternation of Abeta peptide from soluble monomeric alpha-helical form to oligomeric beta-sheet conformation, which may hasten the onset of AD. Abeta42 is more prone to oligomerization compared to Abeta40 in the presence of halothane. The molecular mechanism of halothane induced structural alternation of Abeta peptide is discussed.

Small Amphipathic Molecules Modulate Secondary Structure and Amyloid Fibril-forming Kinetics of Alzheimer Disease Peptide Aβ1–42

“…On the basis of previous work on various other small molecule modulators of A␤ aggregation, such as 8-hydroxyquinolines (42), oleuropein (43,44), ␣-helix stabilizers (45), various chaperones (46,47), anesthetics (48,49), and gangliosides (50), two potential binding sites can be suggested. From these previous studies it is clear that A␤ contains a small molecule binding site near residues 10 -20 and a second binding site in the C-terminal glycine zipper motif.…”

Dilemmas in biomedical research publication

“…Media coverage included statements quoted from the lead author such as 'It is a seriously deadly combination when an older person receives halothane' [33], prompting responses from other researchers in the field [38] and close scrutiny from one or two other interested parties. Serious problems in the two published papers in question were brought to the attention of the editors concerned and the articles were both ultimately retracted, the stated reason being 'misrepresentation' of the data [39,40].…”

Pomegranate Supplementation Protects against Memory Dysfunction after Heart Surgery: A Pilot Study

“…Proposed mechanisms for POCD following heart surgery include general hypoperfusion of the brain (global ischemia), leading to critically low levels of oxygen and glucose throughout the brain, and focal ischemia due to microembolic particles released into the vasculature during surgery [7]. Additionally, inhaled anesthetics have been shown to induce the formation of amyloid-beta, a potentially neurotoxic protein linked to Alzheimer's disease and acute cognitive deficits, in the brain [8–10]. …”