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The Role of Phosphodiesterase-2 in Psychiatric and Neurodegenerative Disorders

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Book cover Phosphodiesterases: CNS Functions and Diseases

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

Abstract

Cyclic nucleotide PDEs are a super-family of enzymes responsible for regulating intracellular levels of the second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Through their catalysis, PDEs are able to exert tight regulation over these important intracellular signaling cascades. Previously, PDEs have been implicated in learning and memory, as well as in mood disorders, such as anxiety and depression. PDE2 is of special interest due to its high level of expression in the forebrain, specifically in the isocortex, entorhinal cortex, striatum, hippocampus, amygdala, and medial habenula. Many of these brain regions are considered participants of the limbic system, which is known as the emotional regulatory center of the brain, and is important for modulating emotion and long-term memory. Therefore, PDE2s coincidental expression in these areas suggests an important role for PDE2 in these behaviors, and researchers are continuing to uncover the complex connections. It was shown that PDE2 inhibitors have pro-cognitive effects in tests of memory, including the object recognition test. PDE2 inhibitors are also protective against cognitive deficits in various models of cognitive impairment. Additionally, PDE2 inhibitors are protective against many different forms of stress-induced anxiety-like and depression-like behaviors. Currently, there is a great need for novel therapeutics for the treatment of mood and cognitive disorders, especially anxiety and depression, and other neurodegenerative diseases, such as Alzheimer’s disease, and PDE2 is emerging as a viable target for future drug development for many of these diseases.

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The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA

    Chong Zhang & James M. O’Donnell

  2. Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA

    Lindsay M. Lueptow

  3. Department of Behavioral Medicine and Psychiatry, West Virginia University Health Sciences Center, 1 Medical Center Drive, Morgantown, WV, 26506, USA

    Han-Ting Zhang

  4. Department of Physiology and Pharmacology, West Virginia University Health Sciences Center, 1 Medical Center Drive, Morgantown, WV, 26506, USA

    Han-Ting Zhang

  5. Institute of Pharmacology, Taishan Medical University, Taian, 271016, China

    Han-Ting Zhang

  6. Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA

    James M. O’Donnell & Ying Xu M.D., Ph.D.

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  1. Chong Zhang
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  3. Han-Ting Zhang
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  5. Ying Xu M.D., Ph.D.
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Correspondence to Ying Xu M.D., Ph.D. .

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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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Zhang, C., Lueptow, L.M., Zhang, HT., O’Donnell, J.M., Xu, Y. (2017). The Role of Phosphodiesterase-2 in Psychiatric and Neurodegenerative Disorders. 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_12

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