文献类型：期刊文献

英文题名：Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement

作者：Wei, Xuemei[1,2];Yu, Guoqi[1,2];Shen, Hualiang[1,2];Luo, Yanjuan[1,2];Shang, Tianbo[1,2];Shen, Runpu[1,2];Xi, Meiyang[1,2];Sun, Haopeng[3]

机构：[1]Shaoxing Univ, Coll Chem & Chem Engn, Shaoxing 312000, Peoples R China;[2]Shaoxing Univ, Zhejiang Engn Res Ctr Fat Soluble Vitamin, Shaoxing 312000, Peoples R China;[3]China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Peoples R China

年份：2023

卷号：130

外文期刊名：BIOORGANIC CHEMISTRY

收录：SCI-EXPANDED(收录号：WOS:000891084600001)、、Scopus(收录号：2-s2.0-85142120693)、WOS

基金：Acknowledgments The authors greatly acknowledge the support from the Zhejiang Province Basic Public Welfare Research Program (No. LGF20H300004) .

语种：英文

外文关键词：PDE4; Cognitive improvement; Subtype selective inhibitors

外文摘要：Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 in-hibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.