| GSK3在抑郁症发病机制中的研究进展 |
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| 引用本文： | 陈姣,;楚世峰,;王真真,;陈乃宏.GSK3在抑郁症发病机制中的研究进展[J].河北北方学院学报(医学版),2014(5):44-54. |
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| 作者姓名： | 陈姣 ;楚世峰 ;王真真 ;陈乃宏 |
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| 作者单位： | [1]中国医学科学院,药物研究所&神经科学中心、天然药物活性物质与功能国家重点实验室,中国北京100050; [2]湖南中医药大学药学院,中国长沙410000 |
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| 基金项目： | 国家自然科学基金资助项目（No.81274122、No.81202507、No.81373998、No.U1402221）; 国家“重大新药创制”科技重大专项项目（No.2012ZX09301002-004）; 北京市自然科学基金项目（No.7131013、No.7142115）; 教育部博士点基金重点项目（No.20121106130001）; 新药作用机制研究与药效评价北京市重点实验室资助项目（No.BZ0150）; 中央级公益性科研院所基本科研业务费专项资金项目（No.2014RC03） |
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| 摘 要： | 尽管锂制剂在临床上使用了几十年,但其确切机制并不清楚。人们通过研究认识到锂可能是通过抑制糖原合成酶激酶3（glycogen synthase kinase 3,GSK3）而发挥抗抑郁作用的。锂可以调控GSK3下游的许多分子,许多抗抑郁类药物可以调控GSK3的信号。使用药理方法或基因沉默方法抑制GSK3均具有稳定情绪、抵抗抑郁的作用,这些研究表明GSK3可能是抗抑郁的潜在靶点。近些年来对GSK3在神经生物学中的作用机制的研究进一步证实了锂可能是通过作用于GSK3来达到治疗目的的。如GSK3可以调节生物体应激反应、炎症反应、神经发生、5-羟色胺（5-hydroxytryptamin,5-HT）传递过程,并参与生物周期节律的调控。因此,特异的GSK3抑制剂能否在临床上发挥抗抑郁作用有待进一步研究。该文对GSK3在应激反应、炎症反应、神经发生、5-HT传递过程以及生物周期节律这五个方面对抑郁发病机制的研究进行了综述。
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| 关 键 词： | GSK3抑制剂 抑郁症 炎症 神经发生 周期节律 |
Research Progress of GSK3 in the Pathophysiology of Depression Disorder |
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| Institution: | CHEN Jiao, CHU Shi-feng, WANG Zhen-zhen, CHEN Nai-hong(1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines,Institute of Materia Medica,Neuroscienee Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China 2. College of Pharmacy,Traditional Chinese Medicine of Hunan University,Changsha,410000,China) |
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| Abstract: | Despite many decades of clinical useness,the therapeutic target of lithium remains uncertain.It is recognized that therapeutic concentrations of lithium is to inhibit the activity of glycogen synthase kinase 3 （GSK3）to treat depression disorder. Specifically,it has been demonstrated that lithium administration regulates multiple GSK3 targets and multiple antidepressant drugs regulate GSK3 signaling. Pharmacological and genetic inhibition of GSK3 results in mood stabilizer-like and antidepressant-like behavior in rodent models. These studies implicate that GSK3 is a possible target for treatment of mood disorders. Furthermore,numerous recent studies have provided more complete understanding of the role of GSK3 in diverse neurological processes, strengthening the hypothesis that GSK3 may represent a therapeutically relevant target of lithium. For example, GSK3 is a primary regulator of oxidative stress response. Inflammatory response,neurogenesis, serotonin transmission and circadian rhythms may be involved in GSK3-regulated pathways. In this regard, further study is needed to develop novel specific GSK3 inhibitors for the treatment of depressive disorders. In this article,we will discuss the role of GSK3 in five aspects including oxidative stress response,inflammatory response, neurogenesis, serotonin transmission and circadian rhythms to summary the research progress in pathological mechanisms of depression. |
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| Keywords: | GSK3 inhibitor depressive disorders inflammation neurogenesis circadianrhythm |
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