Molecular Neurobiology

, Volume 41, Issue 2, pp 129–137

Cyclic GMP and Nitric Oxide Synthase in Aging and Alzheimer's Disease

  • Katarzyna Urszula Domek-Łopacińska
  • Joanna B. Strosznajder

DOI: 10.1007/s12035-010-8104-x

Cite this article as:
Domek-Łopacińska, K.U. & Strosznajder, J.B. Mol Neurobiol (2010) 41: 129. doi:10.1007/s12035-010-8104-x


Cyclic guanosine monophosphate (cGMP) is an important secondary messenger synthesized by the guanylyl cyclases which are found in the soluble (sGC) and particular isoforms. In the central nervous system, the nitric oxide (NO)-sensitive sGC isoform is the major enzyme responsible for cGMP synthesis. Phosphodiesterases (PDEs) are enzymes for hydrolysis of cGMP in the brain, and they are mainly isoforms 2, 5, and 9. The NO/cGMP signaling pathway has been shown to play an important role in the process underlying learning and memory. Aging is associated with an increase in PDE expression and activity and a decrease in cGMP concentration. In addition, aging is also associated with an enhancement of neuronal NO synthase, a lowering of endothelial, and no alteration in inducible activity. The observed changes in NMDA receptor density along with the Ca2+/NO/cGMP pathway underscore the lower synaptic plasticity and cognitive performance during aging. This notion is in agreement with last data indicating that inhibitors of PDE2 and PDE9 improve learning and memory in older rats. In this review, we focus on recent studies supporting the role of Ca2+/NO/cGMP pathway in aging and Alzheimer's disease.


AgingAlzheimer's diseaseBrainCyclic GMPMemoryNitric oxidePhosphodiesterases



Alzheimer's disease


Central nervous system


Cyclic GMP




cGMP-Dependent protein kinase G


Guanylyl cyclase (soluble isoform)


NO synthase

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Katarzyna Urszula Domek-Łopacińska
    • 1
  • Joanna B. Strosznajder
    • 1
  1. 1.Department of Cellular Signaling, M. Mossakowski Medical Research CenterPolish Academy of SciencesWarsawPoland