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Both preclinical and clinical data suggest that elevated <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> signalling may be involved in the aetiology of major diseases such as depression, Alzheimer's disease and diabetes mellitus. <jats:bold>2<\/jats:bold> The molecular pathways by which <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> may cause the manifestation of disease remain poorly understood, although they may include G protein\u2010coupled receptor modulation of the Ras\/<jats:styled-content style=\"fixed-case\">MAP<\/jats:styled-content> kinase, Stat3 and <jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3K pathways, among others. In both individual animals and humans, <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> tone may be elevated largely due to genetics, but also because of the exposure to marked psychological stress or trauma, or other environmental factors. <jats:bold>3<\/jats:bold> As <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> is involved in the \u2018fight or flight\u2019 response by the sympathetic nervous system, this transmitter may be elevated in a large number of organisms due to evolutionary selection of enhancing responses to immediate environmental dangers. Likewise, acetylcholine signalling by the parasympathetic (\u2018rest and digest\u2019) nervous system may be relatively diminished. This putative autonomic imbalance may result in diminished engagement in homeostatic processes, resulting in the emergence and progression of a number of diseases throughout the body. <jats:bold>4<\/jats:bold> In this scenario, a large number of individuals may benefit from chronic use of pharmacological agents \u2013 such as clonidine, guanfacine, propranolol or prazosin \u2013 that diminish <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> signalling throughout the body. If so, <jats:styled-content style=\"fixed-case\">NA<\/jats:styled-content> transmission lowering drugs may protect against a wide range of diseases.<\/jats:p>","DOI":"10.1111\/aap.12019","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T11:26:12Z","timestamp":1412162772000},"page":"15-26","source":"Crossref","is-referenced-by-count":17,"title":["Noradrenaline transmission reducing drugs may protect against a broad range of diseases."],"prefix":"10.1111","volume":"34","author":[{"given":"P. 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