Phosphodiesterase 7 as a therapeutic target – Where are we now?

Zorn, A. and Baillie, G. (2023) Phosphodiesterase 7 as a therapeutic target – Where are we now? Cellular Signalling, 108, 110689. (doi: 10.1016/j.cellsig.2023.110689) (PMID:37120115)

Abstract

Cyclic nucleotide phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyse the intracellular second messengers cAMP and cGMP to their inactive forms 5’AMP and 5’GMP. Some members of the PDE family display specificity towards a single cyclic nucleotide messenger, and PDE4, PDE7, and PDE8 specifically hydrolyse cAMP. While the role of PDE4 and its use as a therapeutic target have been well studied, less is known about PDE7 and PDE8. This review aims to collate the present knowledge on human PDE7 and outline its potential use as a therapeutic target. Human PDE7 exists as two isoforms PDE7A and PDE7B that display different expression patterns but are predominantly found in the central nervous system, immune cells, and lymphoid tissue. As a result, PDE7 is thought to play a role in T cell activation and proliferation, inflammation, and regulate several physiological processes in the central nervous system, such as neurogenesis, synaptogenesis, and long-term memory formation. Increased expression and activity of PDE7 has been detected in several disease states, including neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's disease, autoimmune diseases such as multiple sclerosis and COPD, and several types of cancer. Early studies have shown that administration of PDE7 inhibitors may ameliorate the clinical state of these diseases. Targeting PDE7 may therefore provide a novel therapeutic strategy for targeting a broad range of disease and possibly provide a complementary alternative to inhibitors of other cAMP-selective PDEs, such as PDE4, which are severely limited by their side-effects.

• Item Type: Articles
• Additional Information: This work was supported by the Medical Research Council Doctoral Training Programme in Precision Medicine (grant number: MR/W006804/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Zorn, Alina and Baillie, Professor George

Creator Roles

Zorn, A.: Conceptualization, Investigation, Visualization, Writing – original draft
Baillie, G.: Writing – review and editing

• Authors: Zorn, A., and Baillie, G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Cellular Signalling
• Publisher: Elsevier
• ISSN: 0898-6568
• ISSN (Online): 1873-3913
• Published Online: 28 April 2023
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Cellular Signalling 108:110689
• Publisher Policy: Reproduced under a Creative Commons license