Targeting NO/cGMP Signaling in the CNS for Neurodegeneration and Alzheimer's Disease

Curr Med Chem. 2016;23(24):2770-2788. doi: 10.2174/0929867323666160812145454.


cAMP-response element-binding protein (CREB) plays a central role in various aspects of central nervous system (CNS) function, ranging from the developmental stages to neuronal plasticity and survival in adult brain. Activation of CREB plays a crucial role in learning and memory and is at the convergence of multiple intracellular signaling cascades including CAMKII and MAPK. This review focuses on the important functions of nitric oxide (NO) in activating CREB via the NO receptor, soluble guanylyl cyclase (sGC), and production of the second messenger, cGMP. The involvement of the NO/cGMP signaling pathway in synaptic plasticity suggests several avenues for therapeutic intervention, and targeting early synaptic degeneration could be an attractive approach for the development of novel disease-modifying approaches to treat cognition and memory dysfunction in neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • CREB-Binding Protein / metabolism
  • Central Nervous System / metabolism*
  • Cyclic GMP / metabolism*
  • Humans
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology*
  • Neuronal Plasticity / physiology
  • Nitric Oxide / metabolism*
  • Phosphoric Diester Hydrolases / chemistry
  • Phosphoric Diester Hydrolases / metabolism
  • Signal Transduction
  • Soluble Guanylyl Cyclase / antagonists & inhibitors
  • Soluble Guanylyl Cyclase / metabolism
  • Synapses / metabolism


  • Nitric Oxide
  • CREB-Binding Protein
  • Phosphoric Diester Hydrolases
  • Soluble Guanylyl Cyclase
  • Cyclic GMP