Hippo信号通路及其相关miRNA在阿尔茨海默病与帕金森病中的潜在作用机制  

The Potential Mechanism of Hippo Signaling Pathway and Its Related miRNA Intervention in Alzheimer’s Disease and Parkinson’s Disease

作　　者：刘醒然 张蒙 寇现娟[1,2] LIU Xing-Ran;ZHANG Meng;KOU Xian-Juan(College of Sports Medicine,Wuhan Sports University,Wuhan 430079,China;Hubei Key Laboratory of Sport Training and Monitoring,Wuhan 430079,China;College of Physical Education and Health,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]武汉体育学院运动医学院,武汉430079 [2]运动训练监控湖北省重点实验室,武汉430079 [3]广西医科大学体育与健康学院,南宁530021

出　　处：《生物化学与生物物理进展》2024年第7期1485-1509,共25页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81601228);湖北省自然科学基金创新发展联合基金项目(2024AFD242);广西高校中青年教师科研基础能力提升项目(2023KY0130)资助。

摘　　要：以阿尔茨海默病(Alzheimer’s disease,AD)和帕金森病(Parkinson’s disease,PD)为代表的神经退行性疾病主要特征是神经元进行性的不可逆丢失,导致不同程度的病理变化和认知功能的丧失,目前仍无有效的治疗方法。随着全球老龄化问题的加重,神经退行性疾病的患病人数正在快速上升,已发展成为严重的全球公共卫生事件,迫切需要开发有效的治疗手段。Hippo信号通路是一种高度进化保守的途径,在细胞增殖、分化、发育以及凋亡等生物过程中发挥重要作用,并与miRNA互相作用产生广泛的生物效应,在多种疾病的发生中发挥作用。但在神经退行性疾病中对Hippo信号通路与miRNA的探讨相对缺乏。本文通过梳理Hippo信号通路以及相关miRNA在AD与PD中的作用机制,探讨其内在联系,以期拓展神经退行性疾病的治疗视野,为神经退行性疾病的防治提供新的思路和视角。The main characteristics of neurodegenerative diseases represented by Alzheimer’s disease(AD)and Parkinson’s disease(PD)is the progressive irreversible loss of neurons,leading to varying degrees of pathological changes and loss of cognitive function.There is still no effective treatment.With the acceleration of global aging society,the incidence of neurodegenerative diseases is rapidly increasing,becoming a serious global public health concern that urgently requires the development of effective therapeutic strategies.The Hippo signaling pathway,a highly evolutionarily conserved pathway,consists of the core components MST1/2,LATS1/2,and downstream effectors,transcriptional co-activators YAP and TAZ.It plays a crucial role in the regulation of various biological processes such as cell proliferation,differentiation,development,and apoptosis.Dysregulation of the Hippo pathway contributes to the development of many diseases,including cancer,cardiovascular diseases,immune disorders,etc.Therefore,targeting the dysregulated components of the Hippo pathway may be an effective strategy for treating various diseases.Increasing evidence indicates that the Hippo pathway is excessively activated in the development of neurodegenerative diseases,manifested by increased expression of MST1 and downregulation of YAP.Stabilizing the Hippo pathway levels has shown improvements in AD and PD.However,most studies on the Hippo pathway in AD and PD focus on changes in the expression levels of Hippo pathway components,and research in other neurodegenerative diseases is still lacking.Therefore,further investigation is needed to fully understand the mechanistic role of the Hippo pathway in neurodegenerative diseases.Meanwhile,miRNA,similarly dysregulated in neurodegenerative diseases and serving as biomarkers,is a primary target for miRNA therapy in neurodegenerative diseases,including AD and PD.Activating or inhibiting dysregulated miRNAs is the main strategy of miRNA therapy during the neurodegenerative disease development.Evidence sug

关 键 词：衰老 神经退行性疾病 Hippo信号通路 哺乳动物STE20样激酶1 Yes相关蛋白 

分 类 号：Q189[生物学—神经生物学] Q426[生物学—普通生物学] R592[医药卫生—老年医学]