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Trends Neurosci. 2015 Jul;38(7):448-58. doi: 10.1016/j.tins.2015.05.007. Epub 2015 Jun 20.

Checks and balances on cholinergic signaling in brain and body function.

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Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel; Department of Biological Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Jerusalem 91904, Israel. Electronic address:


A century after the discovery of acetylcholine (ACh), we recognize both ACh receptors, transporters, and synthesizing and degrading enzymes and regulators of their expression as contributors to cognition, metabolism, and immunity. Recent discoveries indicate that pre- and post-transcriptional ACh signaling controllers coordinate the identity, functioning, dynamics, and brain-to-body communication of cholinergic cells. Checks and balances including epigenetic mechanisms, alternative splicing, and miRNAs may all expand or limit the diversity of these cholinergic components by consistently performing genome-related surveillance. This regulatory network enables homeostatic maintenance of brain-to-body ACh signaling as well as reactions to nicotine, Alzheimer's disease anticholinesterase therapeutics, and agricultural pesticides. Here I review recent reports on the functional implications of these controllers of cholinergic signaling in and out of the brain.


acetylcholine signaling; miRNA regulation; noncoding SNPs; post-transcriptional changes

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