Phosphodiesterase Inhibition in Cognitive Decline

Issue title: Alzheimer's Disease: Detection, Prevention, and Preclinical Treatment

Guest editors: Jack C. de la Torre

Article type: Review Article

Authors: García-Barroso, Carolina^a | Ugarte, Ana^b | Martínez, Martín^c | Rico, Alberto J.^{d; f} | Lanciego, José Luis^{d; f} | Franco, Rafael^{a; 2} | Oyarzabal, Julen^b | Cuadrado-Tejedor, Mar^{a; e; 1} | García-Osta, Ana^{a; 1; *}

Affiliations: [a] Neurobiology of Alzheimer's disease, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain | [b] Small Molecule Discovery Platform, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain | [c] Neuroimaging Laboratory, Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain | [d] Neurosciences Division, Centre for Applied Medical Research, CIMA, University of Navarra, Pamplona, Spain | [e] Department of Anatomy, University of Navarra, Pamplona, Spain | [f] Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Spain

Correspondence: [*] Correspondence to: Ana García-Osta, Division of Neurosciences, CIMA, University of Navarra, Av. Pio XII 55, 31008 Pamplona, Spain. Tel.: +34 011 34 948 19 47 00 (2023); Fax: +34 011 34 948 19 47 15, E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] Present address: Department of Biochemistry and Molecular Biology, Universitat de Barcelona, Barcelona, Spain.

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.

Keywords: Cerebrospinal fluid, cGMP, memory enhancement, phosphodiesterase, tadalafil

DOI: 10.3233/JAD-141341

Journal: Journal of Alzheimer's Disease, vol. 42, no. s4, pp. S561-S573, 2014