Nuevas aproximaciones terapéuticas para la Enfermedad de Alzheimer: inhibidores de PDE5 [Tesis]

tesisSe ha introducido en Dadun una nueva Tesis Doctoral:

Título: Nuevas aproximaciones terapéuticas para la Enfermedad de Alzheimer: inhibidores de PDE5

AutoraGarcía Barroso, Carolina

Directoras:  García Osta, Ana y Cuadrado Tejedor, Mar

Resumen: Previous studies have demonstrated that cognitive function can be restored in mouse models of Alzheimer’s disease (AD) following administration of sildenafil, a specific PDE5 inhibitor. Another very potent PDE5 inhibitor with a longer half-life and safe in chronic treatments, tadalafil, may represent a better alternative candidate for AD therapy. In this project we first measured the blood and brain levels of tadalafil to prove for the first time that the compound crosses BBB and that chronic treatment leads to accumulation in the brain of the J20 transgenic mouse model of AD. We demonstrated the presence of PDE5 mRNA in the brain of the mice and also in the human brain. After a 10 week treatment with either of these PDE5 inhibitors, the cognition of the J20 mice improved when compared with the transgenic mice that received vehicle. Biochemical analysis revealed that neither sildenafil nor tadalafil altered the amyloid burden, although both compounds reduced Tau phosphorylation in the […]

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