Phosphodiesterase 2A (PDE2A) (PDE2A)

Phosphodiesterase 2A (PDE2A), historically known as cGMP-stimulated 3',5'-cyclic phosphodiesterase, is a dual-substrate enzyme that hydrolyzes both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (UniProt: O00408). It is uniquely characterized by its allosteric GAF-B domain, which binds cGMP to stimulate the catalytic activity of the enzyme, facilitating vital crosstalk where elevated cGMP levels regulate the rate of cAMP degradation (PubMed: 28414055). Highly expressed in the brain (hippocampus and cortex), adrenal glands, and heart, PDE2A plays a critical role in modulating synaptic plasticity, memory formation, and cardiac function. In the central nervous system, it is investigated as a therapeutic target for cognitive disorders like Alzheimer's disease and anxiety-like behaviors (PubMed: 25995166). In the cardiovascular system, its inhibition is explored for managing heart failure and pulmonary hypertension due to its influence on myocardial contractility and vasodilation (PubMed: 25103491). Current therapeutic development focuses on selective inhibitors such as Lu AF11167 and PF-05180999, though safety monitoring is required due to the enzyme's involvement in adrenal hormone regulation and cardiovascular stability.

Other names

cGMP-stimulated 3',5'-cyclic phosphodiesterasecGMP-stimulated phosphodiesterasePDE2CGS-PDECyclic GMP-stimulated phosphodiesterasePDE2A1PDE2A2PDE2A3EC 3.1.4.17

Selective inhibition of the PDE2A enzyme prevents the hydrolysis of the second messengers cAMP and cGMP, leading to increased intracellular concentrations of these molecules and enhanced downstream signaling in pathways associated with cognitive function and vascular regulation.