PDE3A as a Therapeutic Target for the Modulation of Compartmentalised Cyclic Nucleotide-Dependent Signalling

Phosphodiesterase 3A (PDE3A) hydrolyses cAMP, adjusting cAMP signalling pathways with temporal and spatial accuracy. PDE3A contributes to the control of cAMP in several cellular compartments, including the plasma membrane, the cytosol, or membrane-limited organelles such as the nucleus and the sarcoplasmic reticulum. Through this ability and its expression in various cell types, it regulates a variety of cellular processes like contractility of muscle cells, gene expression, differentiation and proliferation. Dysregulated cAMP signalling causes or is associated with diseases. The therapeutic potential of PDE3A is, however, limited by the lack of specific modulators. Emerging approaches to targeting PDE3A centre on specifically addressing its catalytic domain or its cellular localisation. This review highlights the growing knowledge of PDE3A’s functions in cellular signalling and therapeutic opportunities, opening the door to more fully utilise its potential for the treatment of disease.