The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis.
The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis.
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DOI：
10.1111/j.1399-5618.2009.00714.x
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发表时间：
2009-06
影响因子：
5.4
通讯作者：
Zarate CA Jr
中科院分区：
文献类型：
--
作者：
Machado-Vieira R;Manji HK;Zarate CA Jr
锂一直是并将继续是双相情感障碍（BD）药物治疗急性情绪发作，转换预防，预防性治疗和自杀预防的支柱。锂也是BD的明确概念验证剂，尽管最近在其他精神病以及各种神经退行性疾病中进行了研究。它的神经营养作用可以被看作是一个统一的模型来解释情绪障碍的病理生理学和这些疾病的假定治疗的几个综合方面。增强神经保护（直接涉及神经营养作用）是一种治疗策略，旨在减缓或停止神经元损失的进展，从而通过有利地影响结果和预防疾病发作或临床衰退来产生长期益处。本条：（i）回顾了自凯德最初使用该化合物进行研究以来，关于锂的神经营养作用所学到的知识;（ii）提供了支持BD中细胞萎缩和死亡的存在以及与锂相关的神经营养作用的人体研究数据;（iii）描述了参与这些神经营养作用的锂的关键直接靶点，包括神经营养因子、糖原合成酶激酶3（GSK-3），和线粒体/内质网的关键蛋白质;和（iv）讨论了锂的神经营养作用的模型中的细胞凋亡和兴奋性毒性，以及其潜在的神经营养作用的模型中的神经系统疾病。总之，这里回顾的证据表明，锂在BD中的神经营养作用是一个旧分子作为新概念验证剂的例子。继续破译锂的分子作用的工作可能不仅会导致BD治疗方法的改进，而且会导致神经营养增强剂的开发，这些增强剂可能被证明可用于治疗许多其他疾病。
Lithium has been and continues to be the mainstay of bipolar disorder (BD) pharmacotherapy for acute mood episodes, switch prevention, prophylactic treatment, and suicide prevention. Lithium is also the definitive proof-of-concept agent in BD, although it has recently been studied in other psychoses as well as diverse neurodegenerative disorders. Its neurotrophic effects can be viewed as a unifying model to explain several integrated aspects of the pathophysiology of mood disorders and putative therapeutics for those disorders. Enhancing neuroprotection (which directly involves neurotrophic effects) is a therapeutic strategy intended to slow or halt the progression of neuronal loss, thus producing long-term benefits by favorably influencing outcome and preventing either the onset of disease or clinical decline. The present article: (i) reviews what has been learned regarding lithium’s neurotrophic effects since Cade’s original studies with this compound; (ii) presents human data supporting the presence of cellular atrophy and death in BD as well as neurotrophic effects associated with lithium in human studies; (iii) describes key direct targets of lithium involved in these neurotrophic effects, including neurotrophins, glycogen synthase kinase 3 (GSK-3), and mitochondrial/endoplasmic reticulum key proteins; and (iv) discusses lithium’s neurotrophic effects in models of apoptosis and excitotoxicity as well as its potential neurotrophic effects in models of neurological disorders. Taken together, the evidence reviewed here suggests that lithium’s neurotrophic effects in BD are an example of an old molecule acting as a new proof-of-concept agent. Continued work to decipher lithium’s molecular actions will likely lead to the development of not only improved therapeutics for BD, but to neurotrophic enhancers that could prove useful in the treatment of many other illnesses.
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影响因子：
7.6
作者：
Bearden, Carrie E.;Thompson, Paul M.;Soares, Jair C.
通讯作者：
Soares, Jair C.
影响因子：
11.4
作者：
CADE, JFJ
通讯作者：
CADE, JFJ
DOI：
10.1038/newbio233267a0
发表时间：
1971-01-01
期刊：
NATURE-NEW BIOLOGY
影响因子：
--
作者：
ALLISON, JH;STEWART, MA
通讯作者：
STEWART, MA
影响因子：
6.6
作者：
Brambilla, P;Stanley, JA;Soares, JC
通讯作者：
Soares, JC
影响因子：
2.5
作者：
Benedetti, F;Serretti, A;Smeraldi, B
通讯作者：
Smeraldi, B