PT  - JOURNAL ARTICLE
AU  - Daniela Puzzo
AU  - Agnieszka Staniszewski
AU  - Shi Xian Deng
AU  - Lucia Privitera
AU  - Elena Leznik
AU  - Shumin Liu
AU  - Hong Zhang
AU  - Yan Feng
AU  - Agostino Palmeri
AU  - Donald W. Landry
AU  - Ottavio Arancio
TI  - Phosphodiesterase 5 Inhibition Improves Synaptic Function, Memory, and Amyloid-β Load in an Alzheimer's Disease Mouse Model
AID  - 10.1523/JNEUROSCI.0864-09.2009
DP  - 2009 Jun 24
TA  - The Journal of Neuroscience
PG  - 8075--8086
VI  - 29
IP  - 25
4099  - http://www.jneurosci.org/content/29/25/8075.short
4100  - http://www.jneurosci.org/content/29/25/8075.full
SO  - J. Neurosci.2009 Jun 24; 29
AB  - Memory loss, synaptic dysfunction, and accumulation of amyloid β-peptides (Aβ) are major hallmarks of Alzheimer's disease (AD). Downregulation of the nitric oxide/cGMP/cGMP-dependent protein kinase/c-AMP responsive element-binding protein (CREB) cascade has been linked to the synaptic deficits after Aβ elevation. Here, we report that the phosphodiesterase 5 inhibitor (PDE5) sildenafil (Viagra), a molecule that enhances phosphorylation of CREB, a molecule involved in memory, through elevation of cGMP levels, is beneficial against the AD phenotype in a mouse model of amyloid deposition. We demonstrate that the inhibitor produces an immediate and long-lasting amelioration of synaptic function, CREB phosphorylation, and memory. This effect is also associated with a long-lasting reduction of Aβ levels. Given that side effects of PDE5 inhibitors are widely known and do not preclude their administration to a senile population, these drugs have potential for the treatment of AD and other diseases associated with elevated Aβ levels.