Title:Targeting NO/cGMP Signaling in the CNS for Neurodegeneration and Alzheimer’s Disease
Volume: 23
Issue: 24
Author(s): Manel Ben Aissa, Sue H. Lee, Brian M. Bennett and Gregory R.J. Thatcher
Affiliation:
Keywords:
Alzheimer's disease, CREB activation , NO/cGMP signaling, neuroprotection, synaptic function.
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.
