General anesthetics and β-amyloid protein

Abstract

With roughly 234 million people undergoing surgery with anesthesia each year worldwide, it is important to determine whether commonly used anesthetics can induce any neurotoxicity. Alzheimer's disease (AD) is the most common form of age-related dementia, and a rapidly growing health problem. Several studies suggest that anesthesia could be associated with the development of AD. Moreover, studies in cultured cells and animals show that commonly used inhalation anesthetics may induce changes consistent with AD neuropathogenesis, e.g., β-amyloid protein accumulation. Therefore, in this mini review, we focus on the recent research investigating the effects of commonly used anesthetics including isoflurane, sevoflurane, desflurane, nitrous oxide, and propofol, on Aβ accumulation in vitro and in vivo. We further discuss the future direction of the research determining the effects of anesthetics on β-amyloid protein accumulation.

Keywords: 99-residue membrane-associated C-terminus fragment; AD; AICD; APH-1; APP; APP-C83; APP-C99; APP-CTF; APP-c-terminal fragment; ATP; Adenosine-5'-triphosphate; Alzheimer's disease; Aβ; BACE; BACE cleavage of APP; CAD; DAPT; General anesthetics; IDE; Insulin degrading enzyme; N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester; Neurotoxicity; PEN-2; TNF-α; WT; Z-VAD; amyloid precursor protein; anterior pharynx-defective 1; carbobenzoxy-valyl -alanyl-aspartyl-[Omethyl]- fluromethylketone; carboxyl-terminus fragment of 83 amino acids; coronary artery disease; presenilin enhancer 2; tumor necrosis factor-α; wild-type; α-APPs; α-secretase cleavage of APP; β-APPs; β-Amyloid protein; β-amyloid precursor protein intracellular domain; β-amyloid protein; β-site APP-cleaving enzyme.

Figure 1. Generation of Aβ

APP is cleaved by BACE to generate APP-C99. APP-C99 is further cleaved to release 4-kDa Aβ and β-amyloid precursor protein intracellular domain (AICD) by γ-secretase, which consists of at least four proteins, presenilin 1/presenilin 2, nicastrin, APH-1, and PEN-2.