Phosphodiesterase 4 as a target for the development of novel drugs against cognitive impairment:research advances
10.13220/j.cnki.jipr.2016.01.008
- VernacularTitle:磷酸二酯酶4作为改善认知药物作用靶点的研究进展
- Author:
Haitao WANG
;
Jiangping XU
- Publication Type:Journal Article
- Keywords:
phosphodiesterase;
learning and memory;
cAMP response-element binding protein(CREB);
brain derived neu-rotrophic factor(BDNF);
Alzheimer′s disease
- From:
Journal of International Pharmaceutical Research
2016;(1):44-49
- CountryChina
- Language:Chinese
-
Abstract:
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.
