Emerging roles of CREB-regulated transcription coactivators in brain physiology and pathology

© 2017 Elsevier Ltd 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. CRTCs are novel regulators of neuronal circuits and brain–body communication. CRTC1 regulates neuroplasticity genes involved in synaptic plasticity, memory, and emotional processes. CRTC1 dysfunction is linked to psychiatric and age-related neurodegenerative diseases. CRTCs are novel potential genetic factors and therapeutic targets for psychiatric and neurodegenerative diseases.