CREB 调节转录共激活因子在脑生理学和病理学中的新兴作用。
Emerging Roles of CREB-Regulated Transcription Coactivators in Brain Physiology and Pathology.
机构信息
Institut de Neurociències, Department de Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, Barcelona, Spain.
Center for Psychiatric Neuroscience and Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Switzerland.
出版信息
Trends Neurosci. 2017 Dec;40(12):720-733. doi: 10.1016/j.tins.2017.10.002. Epub 2017 Oct 30.
The brain has the ability to sense, coordinate, and respond to environmental changes through biological processes involving activity-dependent gene expression. cAMP-response element binding protein (CREB)-regulated transcription coactivators (CRTCs) have recently emerged as novel transcriptional regulators of essential biological functions, while their deregulation is linked to age-related human diseases. In the brain, CRTCs are unique signaling factors that act as sensors and integrators of hormonal, metabolic, and neural signals contributing to brain plasticity and brain-body communication. In this review, we focus on the regulatory mechanisms and functions of CRTCs in brain metabolism, lifespan, circadian rhythm, and synaptic mechanisms underlying memory and emotion. We also discuss how CRTCs deregulation in cognitive and emotional disorders may provide the basis for potential clinical and therapeutic applications in neurodegenerative and psychiatric diseases.
大脑通过涉及活性依赖性基因表达的生物过程具有感知、协调和响应环境变化的能力。环磷腺苷反应元件结合蛋白 (CREB)-调节转录共激活因子 (CRTCs) 最近作为基本生物功能的新型转录调节剂出现，而它们的失调与与年龄相关的人类疾病有关。在大脑中，CRTCs 是独特的信号因子，作为激素、代谢和神经信号的传感器和整合器，有助于大脑可塑性和脑体通讯。在这篇综述中，我们重点介绍 CRTCs 在大脑代谢、寿命、昼夜节律以及记忆和情绪的突触机制中的调节机制和功能。我们还讨论了认知和情绪障碍中 CRTCs 的失调如何为神经退行性和精神疾病的潜在临床和治疗应用提供基础。
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