磷酸二酯酶-4的中枢功能研究进展

Research progress of PDE4 in the central nervous system

磷酸二酯酶-4(phosphodiesterase-4,PDE4)对细胞内环腺苷酸(cyclic adenosine monophosphate,cAMP)浓度及其下行信号传导具有重要调控作用,是近年来备受关注的新型药物治疗靶点。PDE4在中枢神经系统具有广泛表达,其4个亚型的分布和功能各具特征。国内外近期研究发现,PDE4在抑郁、认知记忆障碍、药物依赖、神经损伤等疾病进程中发挥重要作用。特异性PDE4抑制剂的研发,可为上述疾病的治疗提供新的路径。该文就近年来PDE4中枢功能的研究进展作一简要综述,并探讨其作为神经精神疾病新型治疗靶点的应用前景。

Phosphodiesterase-4 （PDFA） has been one of the most popular drug targets during recent years due to its critical role in the control of intraeellular cyclic adenosine monophos- phate （cAMP） concentration and downstream signal transduc- tion. PDE4 is widely distributed in the central nervous system （CNS） with different expression levels of its four subtypes. Re- cent data indicate that altered PDE4 expression and/or activity is relevant to multiple CNS disorders, such as depression, memory deficiency, drug dependence, and neural lesion. Selective PDE4 inhibitors exhibit therapeutic effects on these disorders and might be a promising pharmacotherapy. The paper highlights recent re- search progress in the roles of PDFA in CNS function, and dis- cusses the prospects of PDE4 as a novel therapeutic target for CNS disorders.