Targeting NO/cGMP Signaling in the CNS for neurodegeneration and Alzheimer's disease

Manel Ben Aissa, Sue H. Lee, Brian M. Bennett, Gregory R.J. Thatcher

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2770-2783
Number of pages14
JournalCurrent medicinal chemistry
Volume23
Issue number24
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Keywords

  • Alzheimer's disease
  • CREB activation
  • Neuroprotection
  • NO/cGMP signaling
  • Synaptic function

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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