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Current Pharmaceutical Design


ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

The Roles of Phosphodiesterase 2 in the Central Nervous and Peripheral Systems

Author(s): Chong Zhang, Yingcong Yu, Lina Ruan, Chuang Wang, Jianchun Pan, Jonathan Klabnik, Lindsay Lueptow, Han-Ting Zhang, James M. O’Donnell and Ying Xu

Volume 21, Issue 3, 2015

Page: [274 - 290] Pages: 17

DOI: 10.2174/1381612820666140826115245

Price: $65


Phosphodiesterase 2 (PDE2) is a ubiquitous enzyme whose major role is to hydrolyze the important second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In the central nervous system, pharmacological inhibition of PDE2 results in boosted cAMP and/or cGMP signaling, which is responsible for series of changes in protein expression relevant to psychiatric and learning and memory disorders, such as depression, anxiety, and cognition deficits in Alzheimer’s disease. In the periphery, inhibition of PDE2 exhibits beneficial effects in the diseased cardiovascular system, the respiratory system, skeletal muscles and Candida albicans-caused systemic infections. Even though blood-brain barrier penetration properties and selectivity of currently available PDE2 inhibitors have hindered them from entering clinical trials, PDE2 is still of great potential therapeutic values in different categories of diseases, and there is demand for development of new generation drugs targeting PDE2 for treatment of diseases in central nervous and peripheral systems.

Keywords: Phosphodiesterase 2 (PDE2), cyclic AMP (cAMP), cyclic GMP (cGMP), emotion, cognition, cardiovascular health, respiratory health, systemic infection.

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