QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, June 24, 2009, 29(25):8075-8086; doi:10.1523/JNEUROSCI.0864-09.2009

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Puzzo, D. Articles by Arancio, O. PubMed PubMed Citation Articles by Puzzo, D. Articles by Arancio, O.

 Previous Article  |  Next Article 

Development/Plasticity/Repair
Phosphodiesterase 5 Inhibition Improves Synaptic Function, Memory, and Amyloid-β Load in an Alzheimer's Disease Mouse Model

Daniela Puzzo,^1,3 Agnieszka Staniszewski,¹ Shi Xian Deng,² Lucia Privitera,^1,3 Elena Leznik,¹ Shumin Liu,¹ Hong Zhang,¹ Yan Feng,¹ Agostino Palmeri,³ Donald W. Landry,² and Ottavio Arancio^1,2

¹Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, and ²Department of Medicine, Columbia University, New York, New York 10032, and ³Department of Physiological Sciences, University of Catania, Catania 95125, Italy

Correspondence should be addressed to Dr. Ottavio Arancio, Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032. Email: oa1{at}columbia.edu

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.

---

Received Feb. 19, 2009; revised April 21, 2009; accepted May 18, 2009.

Correspondence should be addressed to Dr. Ottavio Arancio, Department of Pathology and Cell Biology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032. Email: oa1{at}columbia.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help