AUTHOR=Knorr Debbra Y. , Demirbas Defne , Heinrich Ralf TITLE=Multifaceted promotion of apoptosis by acetylcholinesterase JOURNAL=Frontiers in Cell Death VOLUME=2 YEAR=2023 URL=https://www.frontiersin.org/journals/cell-death/articles/10.3389/fceld.2023.1169966 DOI=10.3389/fceld.2023.1169966 ISSN=2813-5563 ABSTRACT=

Elevated expression of acetylcholinesterase (AChE) is a common characteristic of apoptotic cells in both invertebrate and vertebrate species. While increased levels of acetylcholinesterase sensitize cells to apoptogenic stimuli, its absence or pharmacological inactivation interferes with apoptotic cell death. acetylcholinesterase may exert its pro-apoptotic function directly as an integral component of the apoptotic molecular machinery or indirectly by limiting the availability of receptor ligands and structural binding partners that promote cell survival under non-apoptogenic conditions. acetylcholinesterase promotes formation of the apoptosome and degrades DNA after nuclear accumulation. Its esterase activity limits the availability of acetylcholine as ligand for cell membrane-located nicotinic and muscarinic ACh-receptors and mitochondrial nicotinic ACh-receptors that normally support vital physiological states. Studies on insects suggest, that cytokine-activated cell-protective pathways may suppress acetylcholinesterase overexpression under apoptogenic conditions to prevent apoptotic cell death. We provide an overview of studies on various organisms and cell types that summarizes the contribution of acetylcholinesterase to the progress of apoptosis via multiple mechanisms.