Zaprinast impairs spatial memory by increasing PDE5 expression in the rat hippocampus

Structural Characterization of Murine Phosphodiesterase 5 Isoforms and Involvement of Cysteine Residues in Supramolecular Assembly

“…We suggested that the progressive accumulation of inactive multimers associated with the reduced hydrolysis of cGMP might be an in vivo cellular physiological mechanism that occurs to respond to this imbalance and to restore cyclic nucleotide homeostasis. Of course, this unbalance may be related to several pathologies, such as those reported in the literature [ 1 , 2 , 4 , 6 , 7 , 9 , 10 , 11 , 12 ].…”

“…Moreover, within each family, multiple gene promoters, alternative splicing and post-translational modifications contribute to increasing the variability and molecular diversity as well as the tissue and cellular distribution [ 1 , 2 , 3 , 4 , 5 ]. Mammalian PDE5 is a known regulator of vascular smooth muscle contraction, and its deregulation has been linked to cardiovascular diseases, cancer, memory loss and cytokine-storm-associated inflammation [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In fact, PDE5 is the molecular target of several well-known drugs used to treat erectile dysfunction, pulmonary hypertension and cardiovascular diseases [ 6 ].…”

Cellular Redox Metabolism Is Modulated by the Distinct Localization of Cyclic Nucleotide Phosphodiesterase 5A Isoforms

“…PDE5 has been identified as the molecular target of several well-known drugs used to treat human diseases such as erectile dysfunction and pulmonary hypertension [ 11 ]. Lately, its action has been extended to learning/memory processes, heart failure, cardio-vascular diseases, human breast and thyroid cancers, and many other pathologies [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ].…”

Cellular redox metabolism is modulated by the distinct localization of cyclic nucleotide phosphodiesterase 5A isoforms

“…The presence of PDE in specific multi-molecular complexes allows the propagation of signals along well-defined pathways, prevents the diffusion of signals and ensures the specificity of downstream biological responses [8]. PDE5, among cGMP-specific hydrolysing families, has been localized in vascular smooth muscle, where it participates in the control of vasodilatation [9,10]; in the last years its action has been extended to learning/memory processes, cardiovascular diseases and cancers [11][12][13][14][15][16][17]. In mammals, 3 isoforms of PDE5 have been identified, called A1, A2 and A3, which show similar cGMP catalytic activities, while differing in the very first N-terminal amino acids [18].…”