Institutional Repository of Key Laboratory of Mental Health, CAS
|其他题名||The JNK signaling pathway as a potential new target for depression|
|卷号||63期号:20页码:1998 ~ 2009|
c-Jun氨基端激酶(c-Jun N-terminal kinase,JNK)属于丝裂原激活的蛋白激酶(mitogen-activated protein kinase,MAPK)家族中受应激激活的一类激酶.众多研究表明,在神经萎缩、炎症反应、氧化应激、心理应激事件中均显著涉及JNK的激活,而这些事件均与抑郁症紧密相联.近年来运用基因敲除和JNK抑制剂等手段证明JNK的确参与抑郁症状的调控;同时不少抗抑郁药的疗效涉及对JNK活性的调节,这些已初步确立JNK与抑郁症之间的关联.本文综述了近年来报道有关JNK与抑郁症关联的研究结果,并全面地考察了其可能的作用机制,涵盖神经萎缩、神经发生、神经突触可塑性、神经炎症、氧化应激、神经兴奋性毒性和糖皮质激素抵抗7个方面,提出确立JNK为靶标进行研究抑郁症的新途径.此外,结合目前围绕JNK进行药物研发和干预JNK途径带来的抗抑郁效果的研究进展,我们认为以JNK为靶标治疗抑郁症具有可观的应用前景.
Depression is a widespread chronic medical illness that can affect thoughts, mood, and physical health. It is characterized by low mood, lack of energy, sadness, insomnia, and an inability to enjoy life. So far, however, clinical studies have shown that patients with depression do not have a satisfactory therapeutic outcome. The pathogenesis of depressive disorder is still not well understood. In recent years, c-Jun N-terminal kinase (JNK) has received more and more recognition for its signaling pathway in the regulation of depression. In this article, we review new research progress in the contribution of JNK signaling to depression and summarize the possible underlying mechanisms. JNK is an important member of the mitogen-activated protein kinases (MAPK) family, and it is also known as stress activated protein kinase because it regulates various responses to environment stresses outside and inside cells. The JNK family has three subtypes of JNK1, JNK2 and JNK3, which are different in tissue expression distribution, activity regulation and function. The pathological factors of depression such as inflammatory stress, oxidative stress and psychological stress can affect the activity of JNK and JNK downstream can regulate the neurodegeneration, neurogenesis, synaptic plasticity, neuroinflammation, glucocorticoid receptor resistance and other related signaling pathways, which are involved in the pathophysiology of depression. Examination of Jnk knockout mice has revealed JNK imposes neurogenesis-dependent control of anxiety behavior. In inflammation-induced models of depression, JNK plays important roles in depressive-like behavior through promoting the expression of proinflammatory cytokines and inflammation-related enzymes. Depressive-like behavior induced by various stress often involves alteration of JNK signaling. For example, the hippocampus in wild-type mice exposed to chronic unpredictable mild stress had higher p-JNK protein expression. Human studies also show dysregulated expression of Jnk gene in blood white cells of depressed patients. All these data indicate that there is a close relationship between JNK and depression. Furthermore, candidate drugs targeting JNK have been developed and showed certain antidepressant effects. However, there are still many problems to be solved in the understanding the regulation mechanisms of JNK in depression. These mainly include: (1) Although there are many literatures on the correlation between JNK and depression, there is not much evidence on whether there is a causal relationship. (2) Although the relationship between JNK1 and depression is relatively clear, JNK2 and JNK3 remain ambiguous. (3) The systemic mechanism of JNK regulating depression needs to be fully revealed on all aspects of the reaction and interaction, including the central nervous system, immune system, endocrine system and so on. (4) The possible side effects of treating depression with JNK as a target need to be evaluated. Future research could be carried out on the above issues. With the development of research based on JNK mechanism, the molecular pathologic nature of depression could be more elucidated. Focusing on JNK as a target may provide new ideas for depression research and bring new strategies and new drug targets for prevention and treatment of depression.
|关键词||抑郁症 C-jun氨基端激酶 神经萎缩 神经发生 突触可塑性 神经炎症 兴奋性毒性 糖皮质激素抵抗|
|张军涛,林文娟. 抑郁症研究和治疗的新靶标:JNK信号通路的作用[J]. 科学通报,2018,63(20):1998 ~ 2009.|
|APA||张军涛,&林文娟.(2018).抑郁症研究和治疗的新靶标:JNK信号通路的作用.科学通报,63(20),1998 ~ 2009.|
|MLA||张军涛,et al."抑郁症研究和治疗的新靶标:JNK信号通路的作用".科学通报 63.20(2018):1998 ~ 2009.|
|抑郁症研究和治疗的新靶标_JNK信号通路（2945KB）||期刊论文||出版稿||限制开放||CC BY-NC-SA||浏览 请求全文|