磷酸二酯酶4抑制剂对阿尔茨海默病、抑郁症及二者共病的潜在治疗作用及其机制研究进展  

Potential therapeutic effect and mechanism of phosphodiesterase-4 inhibitors on Alzheimer disease, depression and their co-diseases: a review

作　　者：丛怡帆 宋双双 侯雪芹 张汉霆 CONG Yi-fan;SONG Shuang-shuang;HOU Xue-qin;ZHANG Han-ting(College of Pharmacy,Shandong First Medical University&Shandong Academy of Medical Sciences,Tai′an 271016,China;College of Pharmacy,Qingdao University,Qingdao 266073,China)

机构地区：[1]山东第一医科大学(山东省医学科学院)药学院,山东泰安271016 [2]青岛大学药学院,山东青岛266073

出　　处：《中国药理学与毒理学杂志》2022年第11期838-850,共13页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81773717);国家自然科学基金(82073827)。

摘　　要：磷酸二酯酶4(PDE4)作为PDE家族中数量最多的一类成员,特异性水解细胞内第二信使环磷酸腺苷(cAMP),并参与多种生理功能的调节,在中枢神经系统疾病的发生发展中发挥重要作用。近年研究表明,PDE4是治疗抑郁症及记忆和认知障碍等神经精神疾患的重要靶点。通过调控PDE4的活性和表达使脑内cAMP表达水平及cAMP介导的信号通路恢复正常,将为阿尔茨海默病、抑郁症及二者共病等神经精神疾病提供重要的治疗策略。本文对PDE4与这些疾病之间关系的最新研究进展进行综述和讨论,为阿尔茨海默病、抑郁症及二者共病的预防和治疗提供新的思路及对策。As the largest member of the phosphodiesterase(PDE) family, type 4 PDE(PDE4) specifically hydrolyzes the intracellular second messenger cyclic adenosine monophosphate(cAMP) and participates in the regulation of various physiological functions, playing an important role in the occurrence and development of central nervous system diseases. Recent studies have shown that PDE4 is an important target for neuropsychiatric disorders such as depression, memory and cognition disorders. By regulating the activity and expression of PDE4, the cellular expression level of cAMP and the signal pathway mediated by cAMP in the brain can be restored to normal, which provides an important therapeutic strategy for neuropsychiatric diseases such as Alzheimer disease(AD), depression, and their co-diseases.This article reviews and discusses the latest research progress in the relationship between PDE4 and these diseases, and offers new ideas and countermeasures for the prevention and treatment of AD, depression, and their co-diseases.

关 键 词：磷酸二酯酶4 阿尔茨海默病 抑郁症 信号通路 环磷酸腺苷 

分 类 号：R964[医药卫生—药理学]