文献类型：期刊文献

中文题名：促分裂原活化的蛋白质激酶(MAPK)在抑郁症中的作用及相关药物研究

英文题名：The Role of MAPK in Depressive Disorder and Research on Related Drugs

作者：王春羽[1,2];刘彦霞[1,2]

第一作者：王春羽

机构：[1]北京联合大学生物化学工程学院食品与医药系,北京100023;[2]北京联合大学生物活性物质与功能食品北京市重点实验室,北京100023

第一机构：北京联合大学生物化学工程学院

年份：2026

卷号：53

期号：2

起止页码：388-403

中文期刊名：生物化学与生物物理进展

外文期刊名：Progress In Biochemistry and Biophysics

收录：;北大核心:【北大核心2023】；

基金：北京联合大学人才强校优选计划(BPHR2019CZ04)资助项目。

语种：中文

中文关键词：抑郁症;促分裂原活化的蛋白质激酶;神经可塑性;炎症反应;药物研究

外文关键词：depressive disorder;mitogen-activated protein kinase;neuroplasticity;inflammatory reaction;drug research

摘要：抑郁症,一种非传染性精神障碍,患病率高、治愈率低、致残率高,是人类共同面对的一大难题。抑郁症发病机制复杂,涉及小胶质细胞过度激活、炎性因子或神经递质水平异常、肠道菌群紊乱等多个方面。促分裂原活化的蛋白质激酶(mitogen-activated protein kinase,MAPK)是一类高度保守的丝氨酸/苏氨酸蛋白激酶,在炎症反应和氧化应激等方面扮演着重要的角色,是维持细胞稳态和调节细胞反应的关键因子。近年来的诸多研究表明,调控MAPK可以影响抑郁症的发生与发展。在MAPK家族中,胞外信号调节激酶(extracellular signal-regulated kinase,ERK)活性异常会导致海马神经元受损,同时驱动小胶质细胞过度活化,进而引发情绪低落,c-Jun氨基端激酶(c-Jun N-terminal kinase,JNK)过度激活作用于海马和前额叶皮层两大情绪调节关键脑区,会引起神经元凋亡,同时抑制神经营养因子的产生,导致神经可塑性被破坏同时加剧抑郁表型,p38则是炎症反应中的关键调节因子,其异常激活可导致中枢神经系统内发生炎症级联反应,持续性神经炎症损伤间接参与抑郁症的发生发展。临床经典药物、新型MAPK抑制剂及某些中药的研发取得了一定进展,可以通过调控MAPK信号通路防治抑郁症。本文对MAPK在抑郁症治疗中的作用进行综述,以期为抑郁症发病机制及新型抗抑郁药物研发提供思路。
Depressive disorder is a prevalent mental illness characterized by pronounced and enduring symptoms of depression and cognitive impairment.The escalating pressures of modern society have led to a corresponding rise in the number of depressive disorder patients,particularly those exposed to adverse social,economic,political,and environmental factors which exacerbate the risk of this disorder.The pathogenesis of depressive disorder is multifaceted,encompassing oxidative stress,neuroplasticity alterations,neuroinflammation,neurotransmitter system imbalances,and intestinal microecological disruptions,among others.Clinically,conventional antidepressants are primarily predicated on the monoamine neurotransmitter hypothesis.This theory posits that depressive disorder can be ameliorated by regulating the levels of neurotransmitters within the body through a singular mechanism.However,the complex and multifaceted pathogenesis of depressive disorder results in limited selectivity for these drugs.Mitogen-activated protein kinase(MAPK)is a conserved serine/threonine kinase that plays a crucial role in various cellular physiological and pathological processes,including cell growth,differentiation,stress adaptation,and inflammatory response.It is instrumental in maintaining cellular homeostasis and regulating cellular responses.Numerous studies indicate that MAPK is involved in the pathogenesis and progression of depressive disorder through various pathogenesis.However,what deserves attention is that the interaction between the pathogenesis and dynamics of regulatory process remains unclear.Modulating MAPK has been shown to influence the onset and progression of depressive disorder,though the precise mechanism remains elusive.Within the MAPK family,aberrant activity of extracellular signal-regulated kinase(ERK)can damage hippocampal neurons and overactivate microglia,precipitating depressive disorder.Excessive activation of c-Jun N-terminal kinase(JNK)results in heightened neuronal apoptosis in the hippocampus and prefrontal cortex,and suppresses the expression of neurotrophic factors.p38,a key regulator in inflammatory reactions,can induce neuroinflammation when overactive,leading to depressive disorder.ERK,JNK,and p38 sub-pathways do not function in isolation but rather interact synergistically and/or antagonistically through shared activators and common target molecules.Consequently,these sub-pathways form a complementary and coordinated regulatory network.In addition,MAPK family members can jointly influence the process of depressive disorder by sharing upstream factors and regulating common downstream targets,and there is a lack of identification of their markers and screening for subgroups.The collective abnormal activities of these MAPK family members illuminate the underlying mechanisms of depressive disorder,suggesting that MAPK could serve as a potential therapeutic target for this disorder.As for the study of ERK,different models of depressive disorder have contradictory effects on its activity.The primary cause of these differences can be attributed to the distinct pathological environments utilized in the creation of depressive disorder models.In the future,it is suggested that we use the inducement of depressive disorder as a modeling standard to accurately simulate the onset of depressive disorder to carry out accurate treatment according to the causes of depressive disorder.Research shows that classic clinical drugs,novel MAPK inhibitors and certain traditional Chinese medicines can prevent and treat depressive disorder by regulating the MAPK signaling pathway.Research on MAPK remains limited,particularly concerning the permeability and cellular specificity across the blood-brain barrier and the identification of objective predictive markers.Although inhibitors face challenges,they also possess significant advantages and developmental potential.This paper systematically summarizes the current status of MAPK in the treatment of depressive disorder,in order to provide insights for researching the pathogenesis of depressive disorder and developing new antidepressant drugs.