Role of phosphodiesterase 5 in synaptic plasticity and memory

Daniela Puzzo^1,2, Salvatore Sapienza¹, Ottavio Arancio², Agostino Palmeri¹

¹Dept of Physiological Sciences, University of Catania, Catania, Italy; ²Dept of Pathology, Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA

Abstract: Phosphodiesterases (PDEs) are enzymes that break down the phosphodiesteric bond of the cyclic nucleotides, cAMP and cGMP, second messengers that regulate many biological processes. PDEs participate in the regulation of signal transduction by means of a fine regulation of cyclic nucleotides so that the response to cell stimuli is both specific and activates the correct third messengers. Several PDE inhibitors have been developed and used as therapeutic agents because they increase cyclic nucleotide levels by blocking the PDE function. In particular, sildenafil, an inhibitor of PDE5, has been mainly used in the treatment of erectile dysfunction but is now also utilized against pulmonary hypertension. This review examines the physiological role of PDE5 in synaptic plasticity and memory and the use of PDE5 inhibitors as possible therapeutic agents against disorders of the central nervous system (CNS).

Keywords: phosphodiesterase 5, NO/cGMP pathway, sildenafil, synaptic plasticity, memory, Alzheimer’s disease