细胞周期蛋白依赖性激酶5的病理学功能及与运动的关系

Pathologic Function of Cyclin-dependent Kinase 5 and Its Relationship With Exercise

细胞周期蛋白依赖性激酶5(cyclin-dependent kinase 5,CDK5)是一种受脯氨酸诱导的丝氨酸/苏氨酸激酶,在脂肪、大脑、血管、心脏以及骨等多个器官组织中表达。早期关于CDK5的研究主要聚焦于神经系统疾病,但近年来随着研究的不断深入,发现CDK5表达升高与代谢性疾病以及肿瘤的发生密切相关。研究表明,CDK5参与调节机体胰岛素分泌、巨噬细胞脂质积累、成骨细胞分化及β淀粉样蛋白和Tau蛋白的形成等多种生物学过程,从而在糖尿病、动脉粥样硬化以及神经退行性疾病等疾病的发病机理中发挥重要作用,同时其活性升高与肿瘤细胞增殖、侵袭密切相关,提示CDK5可能是多种疾病的治疗靶点。运动作为一种低风险、低成本的非药物疗法,可以通过下调CDK5的表达、减少Tau蛋白的形成以及β淀粉样蛋白的沉积,影响神经退行性疾病的发生进程,但是关于CDK5在运动改善疾病的作用中的研究较少,后期还需进一步探究。本文主要对CDK5的病理学功能,以及其与运动之间的关系进行综述,以期为进一步的研究和疾病的诊疗提供依据。

Cyclin-dependent kinases(CDKs)are proline-induced serine/threonine kinases that are primarily involved in the regulation of cell cycle,gene transcription,and cell differentiation.In general,CDKs are activated by binding to specific regulatory subunits of cell cycle proteins and are regulated by phosphorylation of specific T-loops by CDK activated kinases.In the CDKs family,cyclin-dependent kinase 5(CDK5)is a specialized member whose activity is triggered only by interaction with p35 and p39,which do not have the same sequence as the cell cycle proteins,and this may be one reason why CDK5 is distinguished from other CDK members by its structural and functional differences.In addition,unlike most CDK members that require phosphorylation at specific sites to function,CDK5 does not require such phosphorylation,and it can be activated simply by binding to p35 and p39.More notably,inhibitors that are commonly used to inhibit the activity of other CDK members have almost zero effect on CDK5.In contrast,CDK5,as a unique CDK family member,plays an important role in the development of numerous diseases.In metabolic diseases,elevated CDK5 expression leads to decreased insulin secretion,increased foam cell formation and triggers decreased bone mass in the body,thus accelerating metabolic diseases,and the role of CDK5 in bone biology is gradually gaining attention,and the role of CDK5 in bone metabolic diseases may become a hotspot for research in the future;in neurodegenerative diseases,hyperphosphorylation of Tau protein is an important hallmark of Alzheimer’s disease development,and changes in CDK5 expression are associated with Tau protein phosphorylation and nerve death,indicating that CDK5 is highly related to the development of the nervous system;in tumor diseases,the role of CDK5 in the proliferation,differentiation and migration and invasion of tumor cells marks the development of tumorigenesis,but different researchers hold different views,and further studies are needed in the follow-up.Therefore,the study of its mechanism of action in diseases can help to reveal the pathogenesis and pathological process of diseases.Appropriate exercise not only helps in the prevention of diseases,but also plays a positive role in the treatment of diseases.Exercise-induced mechanical stress can improve bone microstructure and increase bone mass in osteoporosis patients.In addition,exercise can effectively inhibit neuronal apoptosis and improve mitochondrial dysfunction,more importantly,appropriate exercise can inhibit the proliferation of cancer cells to a certain extent.It can be seen that exercise occupies a pivotal position in the prevention and treatment of pathologic diseases.It has been shown that exercise can reduce the expression of CDK5 and affect the pathological process of neurological diseases.Currently,there is a dearth of research on the specific mechanisms of CDK5’s role in improving disease outcomes through exercise.In order to understand its effects more comprehensively,subsequent studies need to employ diverse exercise modalities,targeting patients with various types of diseases or corresponding animal models for in-depth exploration.This article focuses on the pathological functions of CDK5 and its relationship with exercise,with a view to providing new insights into the prevention and treatment of disease by CDK5.