Alzheimer′s disease(AD)is one of the most common causes of cognitive impairment.“Aβhypothesis”and“tau protein aggregation hypothesis”are two representative hypotheses in relation to AD pathology. But recently,therapeutic strategy target⁃ing on reducing Aβdeposition failed in clinical trials. On the other hand,as the phosphorylation of tau protein is regulated by multiple upstream kinases,inhibition of a single kinase usually cannot effectively suppress the aggregation of the tau. While blocking multiple kinases at the same time will produce serious side effects. Currently,targeting on Aβand tau protein get into awkward situations. In view of this,researchers are looking for new drug targets for improving cognitive function. Phosphodiesterase 4(PDE4 4)is an enzyme responsible for the hydrolysis of cAMP in the body. There are four subtypes for PDE4,and PDE4A,B and D are highly expressed in the central nervous system. Inhibition of PDE4 causes activation of cAMP/PKA/CREB/BDNF signal pathway,which is beneficial for the strengthening and consolidation of learning and memory. This review will focus on the most recent evidence regarding the role of PDE4 in learning and memory.%阿尔茨海默病（AD）是导致认知功能障碍最常见的疾病之一，“β淀粉样蛋白（Aβ）假说”及“tau蛋白聚集假说”是AD发病机制中比较有代表性的学说。但目前针对减少Aβ沉积的疗法在临床试验中宣告失败；而tau蛋白上游有多个蛋白激酶可调控其磷酸化，抑制单个激酶往往不能有效抑制tau的聚集，同时抑制多个激酶又会产生比较严重的不良反应。目前，以Aβ及tau蛋白为靶点的药物研发均遇到很大的阻力。鉴于此，研究人员正在寻找新的改善认知障碍的药物作用靶点。磷酸二酯酶4（PDE4）是体内负责水解cAMP的酶类，其中PDE4A、B及D在中枢神经系统高度表达。抑制PDE4可引起cAMP/PKA/CREB/BDNF信号通路的活化，从而有利于加强和巩固学习记忆。本文将对PDE4在学习记忆的作用、作用的信号通路及以PDE4为靶点研发改善认知障碍药物的进展做一综述。
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