Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches

Tibbo, A. J., Tejeda, G. S. and Baillie, G. S. (2019) Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches. Biochemical Society Transactions, 47(5), pp. 1557-1565. (doi: 10.1042/BST20190763) (PMID:31642904) (PMCID:PMC6824677)

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Abstract

Phosphodiesterases (PDEs) have long been considered as targets for the treatment of Alzheimer's disease (AD) and a substantial body of evidence suggests that one sub-family from the super-family of PDEs, namely PDE4D, has particular significance in this context. This review discusses the role of PDE4 in the orchestration of cAMP response element binding signaling in AD and outlines the benefits of targeting PDE4D specifically. We examine the limited available literature that suggests PDE4 expression does not change in AD brains together with reports that show PDE4 inhibition as an effective treatment in this age-related neurodegenerative disease. Actually, aging induces changes in PDE4 expression/activity in an isoform and brain-region specific manner that proposes a similar complexity in AD brains. Therefore, a more detailed account of AD-related alterations in cellular/tissue location and the activation status of PDE4 is required before novel therapies can be developed to target cAMP signaling in this disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Tibbo, Miss Amy and Baillie, Professor George and Tejeda, Dr Rer Nat Gonzalo
Authors: Tibbo, A. J., Tejeda, G. S., and Baillie, G. S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Biochemical Society Transactions
Publisher:Portland Press
ISSN:0300-5127
ISSN (Online):1470-8752
Published Online:23 October 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Biochemical Society Transactions 47(5): 1557-1565
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301414Targeting PDE3/4 to allow regulation of cardiac calcium homeostasis in diseaseGeorge BaillieBritish Heart Foundation (BHF)PG/17/26/32881CAMS - Cardiovascular Science
190706Priming Innovative Translational Research - The University of Glasgow CiC ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_13063Institute of Cardiovascular & Medical Sciences
172565Priming Innovative Translational Research - the Glasgow Chemical Biology ProgrammeAnna DominiczakMedical Research Council (MRC)MC_PC_15039Institute of Cardiovascular & Medical Sciences