降低去甲肾上腺素传递的药物可以预防多种疾病。

P. J. Fitzgerald
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引用次数: 16

摘要

越来越多的证据表明,信号分子去甲肾上腺素(NA)在广泛的精神、神经和外周疾病中起着病理生理作用。临床前和临床数据均表明NA信号的升高可能与抑郁症、阿尔茨海默病和糖尿病等重大疾病的病因有关。2 NA可能引起疾病表现的分子途径仍然知之甚少,尽管它们可能包括G蛋白偶联受体调节Ras/MAP激酶、Stat3和PI3K途径等。在个体动物和人类中,NA音调的升高可能主要是由于遗传,但也可能是因为暴露于明显的心理压力或创伤,或其他环境因素。由于NA参与交感神经系统的“战斗或逃跑”反应,由于增强对即时环境危险的反应的进化选择,这种递质可能在大量生物体中升高。同样,副交感神经系统(“休息和消化”)发出的乙酰胆碱信号可能相对减少。这种假定的自主神经失衡可能导致体内平衡过程的减少,从而导致全身许多疾病的出现和发展。在这种情况下,大量个体可能受益于长期使用药物,如可乐定、胍法辛、心得安或哌唑嗪,这些药物可以减少全身NA信号。如果是这样的话,降低NA传播的药物可以预防多种疾病。
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Noradrenaline transmission reducing drugs may protect against a broad range of diseases.

1 A growing body of evidence suggests that the signalling molecule, noradrenaline (NA), plays a pathophysiological role in a broad range of psychiatric, neurological and peripheral disorders. Both preclinical and clinical data suggest that elevated NA signalling may be involved in the aetiology of major diseases such as depression, Alzheimer's disease and diabetes mellitus. 2 The molecular pathways by which NA may cause the manifestation of disease remain poorly understood, although they may include G protein-coupled receptor modulation of the Ras/MAP kinase, Stat3 and PI3K pathways, among others. In both individual animals and humans, NA tone may be elevated largely due to genetics, but also because of the exposure to marked psychological stress or trauma, or other environmental factors. 3 As NA is involved in the ‘fight or flight’ 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 (‘rest and digest’) 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. 4 In this scenario, a large number of individuals may benefit from chronic use of pharmacological agents – such as clonidine, guanfacine, propranolol or prazosin – that diminish NA signalling throughout the body. If so, NA transmission lowering drugs may protect against a wide range of diseases.

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