title: Phosphodiesterase inhibition in cognitive decline.
abstract: Understanding the cellular and molecular processes involved in learning and memory will help in the development of safe and effective cognitive enhancers. The cAMP response element-binding (CREB) may be a universal modulator of processes required for memory formation, and increasing the levels of second messengers like cAMP and cGMP could ultimately lead to CREB activation. Phosphodiesterase (PDE) inhibitors regulate signaling pathways by elevating cAMP and/or cGMP levels, and they have been demonstrated to improve learning and memory in a number of rodent models of impaired cognition. The aim of this review is to summarize the outstanding progress that has been made in the application of PDE inhibitors for memory dysfunction. In addition, we have introduced some recent data we generated demonstrating that tadalafil could be considered as an optimal candidate for drug re-positioning and as a good candidate to enhance cognition.
authors.affiliation: Neurobiology of Alzheimer's disease, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: García-Barroso
authors.affiliation: Small Molecule Discovery Platform, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ugarte
authors.affiliation: Neuroimaging Laboratory, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Martín
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Rico
authors.affiliation: Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Lanciego
authors.affiliation: Neurobiology of Alzheimer's disease, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.affiliation: Small Molecule Discovery Platform, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Julen
authors.initials: J
authors.lastname: Oyarzabal
authors.affiliation: Neurobiology of Alzheimer's disease, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain Department of Anatomy, University of Navarra, Pamplona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Cuadrado-Tejedor
authors.affiliation: Neurobiology of Alzheimer's disease, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: García-Osta
mesh_terms: D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases
keywords: Cerebrospinal fluid; cGMP; memory enhancement; phosphodiesterase; tadalafil