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Use of cholinesterase inhibitors is currently the main treatment option to alleviate symptoms of Alzheimer's disease and has been postulated as a therapeutic strategy in acute brain damage (stroke and traumatic brain injury). However, the benefits of this treatment are still not clear. Importantly, cholinergic receptors are expressed both by neurons and by astrocytes and microglia, and binding of acetylcholine to the \u03b17 nicotinic receptor in glial cells results in anti\u2010inflammatory response. Similarly, the brain fine\u2010tunes the peripheral immune response over the cholinergic anti\u2010inflammatory axis. All of these processes are of importance for the outcome of acute and chronic neurological disease. Here, we summarize the main findings about the role of cholinergic signaling in brain disorders and provide insights into the complexity of molecular regulators of cholinergic responses, such as microRNAs and transfer RNA fragments, both of which may fine\u2010tune the orchestra of cholinergic mRNAs. The available data suggest that these small noncoding RNA regulators may include promising biomarkers for predicting disease course and assessing treatment responses and might also serve as drug targets to attenuate signaling cascades during overwhelming inflammation and to ameliorate regenerative capacities of neuroinflammation.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15332-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.15332","type":"journal-article","created":{"date-parts":[[2021,2,27]],"date-time":"2021-02-27T05:34:06Z","timestamp":1614404046000},"page":"1425-1438","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Regulators of cholinergic signaling in disorders of the central nervous system"],"prefix":"10.1111","volume":"158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3085-9054","authenticated-orcid":false,"given":"Katarzyna","family":"Winek","sequence":"first","affiliation":[{"name":"The Edmond and Lily Safra Center for Brain Sciences The Hebrew University of Jerusalem Jerusalem Israel"},{"name":"The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0955-526X","authenticated-orcid":false,"given":"Hermona","family":"Soreq","sequence":"additional","affiliation":[{"name":"The Edmond and Lily Safra Center for Brain Sciences The Hebrew University of Jerusalem Jerusalem Israel"},{"name":"The Alexander Silberman Institute of Life Sciences The Hebrew University of Jerusalem Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7233-5342","authenticated-orcid":false,"given":"Andreas","family":"Meisel","sequence":"additional","affiliation":[{"name":"Department of Neurology with Experimental Neurology Center for Stroke Research Berlin NeuroCure Clinical Research Center Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2010.00015"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118575"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.002"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2340\/16501977-2040"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12911"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep28148"},{"key":"e_1_2_10_9_1","first-page":"114","article-title":"How close are miRNAs from clinical practice? 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