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Trends Neurosci. 2017 Dec;40(12):720-733. doi: 10.1016/j.tins.2017.10.002. Epub 2017 Oct 30.

Emerging Roles of CREB-Regulated Transcription Coactivators in Brain Physiology and Pathology.

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Institut de Neurociències, Department de Bioquímica i Biologia Molecular, Centro de Investigación Biomédica en Red Enfermedades Neurodegenerativas (CIBERNED), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address:
Center for Psychiatric Neuroscience and Service of Child and Adolescent Psychiatry, Department of Psychiatry, University Medical Center, University of Lausanne, Switzerland. Electronic address:


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.


CREB; major depression; memory; neurodegeneration; synaptic plasticity

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