摘要
cAMP反应子结合蛋白(CREB)在中枢神经系统(CNS)功能的各个方面如从发育阶段到神经元的可塑性方面起着关键作用。CREB的激活在学习和记忆中起着至关重要的作用,并在多种细胞内信号级联如CAMKII和MAPK中具有收敛性。本文主要讨论了一氧化氮(NO)通过NO受体、可溶性鸟苷酸环化酶(SGC)和第二信使cGMP的产生来激活CREB的重要功能。在突触可塑性方面,NO/cGMP信号途径的产生表明治疗干预的几种途径和针对早期的突触变性是发展新型疾病修饰手段的可行方法,该方法可用于治疗神经退行性疾病的认知和记忆功能障碍。
关键词: 阿尔茨海默病,CREB激活,NO/cGMP信号,神经保护、突触功能
Current Medicinal Chemistry
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, Gregory R.J. Thatcher
Affiliation:
关键词: 阿尔茨海默病,CREB激活,NO/cGMP信号,神经保护、突触功能
摘要: 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.
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Cite this article as:
Manel Ben Aissa, Sue H. Lee, Brian M. Bennett, Gregory R.J. Thatcher , Targeting NO/cGMP Signaling in the CNS for Neurodegeneration and Alzheimer’s Disease, Current Medicinal Chemistry 2016; 23 (24) . https://dx.doi.org/10.2174/0929867323666160812145454
DOI https://dx.doi.org/10.2174/0929867323666160812145454 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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