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Phosphodiesterase-4B as a Therapeutic Target for Cognitive Impairment and Obesity-Related Metabolic Diseases

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Phosphodiesterases: CNS Functions and Diseases

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

Abstract

People in modern, affluent societies are living longer but also becoming increasingly overweight. With increased life expectancy comes increased risk of developing age-related cognitive decline and neurodegenerative diseases, such that an increasing proportion of life may be lived with cognitive impairment as age increases. Obesity is associated with poorer cognitive function in elderly subjects, and often leads to ill-health arising from various complications such as metabolic syndrome and type-2 diabetes mellitus. This chapter provides an overview of the effects of administering pan-phosphodiesterase-4 (PDE4) inhibitors to animal models of cognitive ageing, Alzheimer’s disease, frontotemporal dementia, fragile X syndrome, obesity and diabetes. Inhibition of the PDE4B subtype specifically is discussed as an approach to avoid the emetic side effects of pan-PDE4 inhibitors, whilst retaining their therapeutic effects. Finally, the findings of rodent studies that employ genetic and pharmacological approaches to specifically target PDE4B are discussed in relation to the potential utility of PDE4B-selective inhibitors for the treatment of cognitive impairment and obesity-related metabolic diseases.

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  1. School of Biomedical Sciences, University of Leeds, Leeds, LS2 9JT, UK

    Steven J. Clapcote

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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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Clapcote, S.J. (2017). Phosphodiesterase-4B as a Therapeutic Target for Cognitive Impairment and Obesity-Related Metabolic Diseases. 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_5

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