2. Academic Validation
  3. Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement

Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement

  • Bioorg Chem. 2023 Jan;130:106278. doi: 10.1016/j.bioorg.2022.106278.
Xuemei Wei 1,  Guoqi Yu 1,  Hualiang Shen 1,  Yanjuan Luo 1,  Tianbo Shang 1,  Runpu Shen 1,  Meiyang Xi 1,  Haopeng Sun 2
Affiliations

Affiliations

  • 1 College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, 312000, China; Zhejiang Engineering Research Center of Fat-soluble Vitamin, Shaoxing University, Shaoxing, 312000, China.
  • 2 Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, 210009, China. Electronic address: [email protected].
PMID: 36413930 DOI: 10.1016/j.bioorg.2022.106278
Abstract

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 inhibitors 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.

Keywords

Cognitive improvement; PDE4; Subtype selective inhibitors.

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