上海交通大学学报（医学版）

上海交通大学学报（医学版）

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磷酸二酯酶10A及其研究进展

闫军浩1，沈倩诚2，王争1   

  1. 上海交通大学 1.医学院附属仁济医院普外科， 上海 200127； 2.基础医学院细胞分化与凋亡教育部重点实验室， 上海 200025
  • 出版日期:2015-12-28 发布日期:2016-01-21
  • 通讯作者: 王争, 电子信箱: wangzh1972@126.com。
  • 作者简介:闫军浩（1989—）， 男， 硕士生; 电子信箱: yanjh5212014@126.com。

Research progresses of phosphodiesterase 10A

YAN Jun-hao1, SHEN Qian-cheng2, WANG Zheng1   

  1. 1.Department of General Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127,  China; 2.Key Laboratory of the Ministry of Education of Cell Differentiation and Apoptosis, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China
  • Online:2015-12-28 Published:2016-01-21

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摘要：

磷酸二酯酶10A（PDE10A）是磷酸二酯酶第10家族中的唯一成员，水解第2信使cAMP和cGMP，从而参与许多细胞内信号转导通路的调节。PDE10A在大脑纹状体中的高表达，提示其参与纹状体功能障碍相关疾病的发病过程;此外，PDE10A在某些外周疾病相关组织细胞中的表达升高;因此，PDE10A可能在多种疾病的发生和发展过程中发挥着重要作用。尽管PDE10A在医学研究和药物开发中越来越受到关注，但其结构、功能及生理/病理调节机制的研究仍存在诸多问题，特别是PDE10A的选择性抑制剂PF-2545920(MP-10)在治疗精神分裂症临床Ⅱ期试验的失败，促使人们重新审视PDE10A在中枢内的功能以及PDE10A能否真正成为治疗靶点。鉴于此，该文从PDE10A的基本特征、结构与功能和相关疾病等方面进行总结，以期指导对其进行进一步的研究和应用。

关键词: 磷酸二酯酶, 磷酸二酯酶10A, 磷酸二酯酶抑制剂, 纹状体, 精神分裂症, 亨廷顿病

Abstract:

Phosphodiesterase 10A (PDE10A) is the only member of the tenth family of phosphodiesterases and hydrolyzes the ubiquitous second messengers, i.e. cyclic adenosine 3′,5′-monophosphate (cAMP) and cyclic guanosine 3′,5′-monophosphate (cGMP), thus involves in the regulation of a number of intracellular signal transduction pathways. High expression in striatum of brain suggests that PDE10A involves in the development of diseases related to striatal dysfunction. In addition, the PDE10A level of patients with some peripheral diseases significantly increased in the tissue cells. So PDE10A is likely to play an important role in the genesis and development of many diseases. Despite medicine researches and drug development pay more and more attention on PDE10A, a lot of problems still exist in terms of studies on its structure, functions, and regulatory mechanisms of physiology and pathology. Especially the failure of a specific inhibitor of PDE10A, PF-2545920 (MP-10), for the treatment of schizophrenia in phaseⅡ clinical trials drives people to reexamine the roles of PDE10A in central nervous system and whether PDE10A is a suitable therapeutic target. So this paper summarizes the basic characteristics, structure, and functions of PDE10A and related diseases and hopes to be helpful for further study and application.

Key words: phosphodiesterase, phosphodiesterase 10A (PDE10A), phosphodiesterase inhibitors, striatum, schizophrenia, Huntington's disease