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Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimer's disease

Citation

Perez-Gonzalez, R and Pascual, C and Antequera, D and Bolos, M and Redondo, M and Perez, DI and Perez-Grijalba, V and Krzyzanowska, A and Sarasa, M and Gil, C and Ferrer, I and Martinez, A and Carro, E, Phosphodiesterase 7 inhibitor reduced cognitive impairment and pathological hallmarks in a mouse model of Alzheimer's disease, Neurobiology of Aging: Experimental and Clinical Research, 34, (9) pp. 2133-2145. ISSN 0197-4580 (2013) [Refereed Article]

DOI: doi:10.1016/j.neurobiolaging.2013.03.011

Abstract

Elevated levels of amyloid beta (Aβ) peptide, hyperphosphorylation of tau protein, and inflammation are pathological hallmarks in Alzheimer's disease (AD). Phosphodiesterase 7 (PDE7) regulates the inflammatory response through the cyclic adenosine monophosphate signaling cascade, and thus plays a central role in AD. The aim of this study was to evaluate the efficacy of an inhibitor of PDE7, named S14, in a mouse model of AD. We report that APP/Ps1 mice treated daily for 4 weeks with S14 show: (1) significant attenuation in behavioral impairment; (2) decreased brain Aβ deposition; (3) enhanced astrocyte-mediated Aβ degradation; and (4) decreased tau phosphorylation. These effects are mediated via the cyclic adenosine monophosphate/cyclic adenosine monophosphate response element-binding protein signaling pathway, and inactivation of glycogen synthase kinase (GSK)3. Our data support the use of PDE7 inhibitors, and specifically S14, as effective therapeutic agents for the prevention and treatment of AD.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Expanding Knowledge
Objective Group:Expanding Knowledge
Objective Field:Expanding Knowledge in the Biological Sciences
Author:Bolos, M (Dr Marta Bolos Jurado)
ID Code:87494
Year Published:2013
Web of Science® Times Cited:35
Deposited By:Menzies Institute for Medical Research
Deposited On:2013-11-20
Last Modified:2013-11-20
Downloads:0

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