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From Age-Related Cognitive Decline to Alzheimer’s Disease: A Translational Overview of the Potential Role for Phosphodiesterases

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Phosphodiesterases: CNS Functions and Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 17))

Abstract

Phosphodiesterase inhibitors (PDE-Is) are pharmacological compounds enhancing cAMP and/or cGMP signaling. Both these substrates affect neural communication by influencing presynaptic neurotransmitter release and postsynaptic intracellular pathways after neurotransmitter binding to its receptor. Both cAMP and cGMP play an important role in a variety of cellular functions including neuroplasticity and neuroprotection. This chapter provides a translational overview of the effects of different classes of PDE-Is on cognition enhancement in age-related cognitive decline and Alzheimer’s disease (AD). The most effective PDE-Is in preclinical models of aging and AD appear to be PDE2-Is, PDE4-Is and PDE5-Is. Clinical studies are relatively sparse and so far PDE1-Is and PDE4-Is showed some promising results. In the future, the demonstration of clinical proof of concept and the generation of isoform selective PDE-Is are the hurdles to overcome in developing safe and efficacious novel PDE-Is for the treatment of age-related cognitive decline and cognitive dysfunction in AD.

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Conflict of Interest

Arjan Blokland and Jos Prickaerts have a proprietary interest in the PDE4 inhibitor roflumilast. In addition, Jos Prickaerts has a proprietary interest in selective PDE4D inhibitors, including GEBR-related compounds.

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Authors and Affiliations

  1. Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, PO Box 616, 6200, MD, Maastricht, The Netherlands

    Pim R. A. Heckman & Jos Prickaerts

  2. Department of Neuropsychology and Psychopharmacology, Maastricht University, PO Box 616, 6200, MD, Maastricht, The Netherlands

    Pim R. A. Heckman & Arjan Blokland

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  1. Pim R. A. Heckman
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  3. Jos Prickaerts
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Correspondence to Jos Prickaerts .

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  1. Department of Behavioral Medicine and Psychiatry; Department of Physiology and Pharmacology; Institute of Pharmacology, West Virginia University Health Sciences Center; Taishan Medical University, Morgantown; Taian, China, West Virginia, USA

    Han-Ting Zhang

  2. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    Ying Xu

  3. School of Pharmacy and Pharmaceutical Sciences, University at Buffalo The State University of New York, Buffalo, New York, USA

    James M. O'Donnell

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Heckman, P.R.A., Blokland, A., Prickaerts, J. (2017). From Age-Related Cognitive Decline to Alzheimer’s Disease: A Translational Overview of the Potential Role for Phosphodiesterases. In: Zhang, HT., Xu, Y., O'Donnell, J. (eds) Phosphodiesterases: CNS Functions and Diseases. Advances in Neurobiology, vol 17. Springer, Cham. https://doi.org/10.1007/978-3-319-58811-7_6

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