磷酸二酯酶抑制剂与学习记忆相关信号转导通路研究进展

Progress in the relationship of phosphodiesterases inhibitors and signal transduction pathway associated with learning and memory

大量的研究表明,环磷酸腺苷反应元件结合蛋白(cAMP response element binding protein,CREB)直接或间接激活相关基因转录,进而表达c-fos、c-jun、BDNF等,在神经元应激损伤后的再生、存活及修复以及学习记忆等方面发挥重要作用。磷酸二酯酶可以水解环磷酸腺苷(cyclic AMP,cAMP)及环磷酸鸟苷(cyclic GMP,cGMP),进而影响其下游信号转导,发挥对CREB的调节作用。该文从磷酸二酯酶抑制剂与学习记忆相关信号通路的关系及在学习记忆障碍中发挥的作用予以综述,并由该通路入手对发现治疗神经退行性变疾病药物作用新靶点的可能性予以展望。

A large number of studies indicates that cAMP response element binding protein （CREB） directly or indirectly activates the transcription of certain gene such as c-fos, c-inn, BDNF,et al, and then expresses the certain protein molecules and neurotropbic factor, which plays an important role in the renewable, survival and repair of neurons in the stress injury and learning and memory. Phosphodiesterases（PDEs） can hydrolyze cyclic AMP （cAMP）and cyclic （GMP）, affect its downstream signal transduction, and play a role in the regulation of CREB. This article reviews the progress in the relationship of phosphodi- esterases inhibitors and signal transduction pathway associated with learning and memory and the role of its effects on learning and memory disorders, to explore the prospects of phosphodies- terase as new drug targets for neurodegenerative disorders.