Title:The Roles of Phosphodiesterase 2 in the Central Nervous and Peripheral Systems
Volume: 21
Issue: 3
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
Affiliation:
Keywords:
Phosphodiesterase 2 (PDE2), cyclic AMP (cAMP), cyclic GMP (cGMP), emotion, cognition, cardiovascular health, respiratory
health, systemic infection.
Abstract: 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.
