Current Medicinal Chemistry

Atta-ur-Rahman, FRS
Honorary Life Fellow
Kings College
University of Cambridge
Cambridge
UK

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

Author(s): Manel Ben Aissa, Sue H. Lee, Brian M. Bennett, Gregory R.J. Thatcher.

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.

Keywords: Alzheimer's disease, CREB activation , NO/cGMP signaling, neuroprotection, synaptic function.

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Article Details

VOLUME: 23
ISSUE: 24
Year: 2016
Page: [2770 - 2788]
Pages: 19
DOI: 10.2174/0929867323666160812145454
Price: $58