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

Abstract

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.

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Abbreviations

AD:

Alzheimer's disease

CNS:

Central nervous system

cGMP:

Cyclic GMP

PDEs:

Phosphodiesterases

PKG:

cGMP-Dependent protein kinase G

sGC:

Guanylyl cyclase (soluble isoform)

NOS:

NO synthase

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Correspondence to Katarzyna Urszula Domek-Łopacińska.

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Domek-Łopacińska, K.U., Strosznajder, J.B. Cyclic GMP and Nitric Oxide Synthase in Aging and Alzheimer's Disease. Mol Neurobiol 41, 129–137 (2010). https://doi.org/10.1007/s12035-010-8104-x

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Keyword

  • Aging
  • Alzheimer's disease
  • Brain
  • Cyclic GMP
  • Memory
  • Nitric oxide
  • Phosphodiesterases