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Receptor interacting protein 140 (RIP140), gene named Nuclear receptor interacting protein 1 (Nrip1), is a transcription co-regulator of numerous nuclear receptors and transcription factors that are important for various biological processes. RIP140 is highly expressed in various cell types of the brain, especially cortex and hippocampus. Increasingly, studies have begun to reveal its multiple functional roles in maintaining brain health. In particularly, there appears to be an intimate relationship between RIP140 and neurodegenerative diseases, such as reduced RIP140 expression in Alzheimer’s Disease (AD) postmortem brain and impaired cognitive functions in RIP140 knockout mice. The different functional roles of RIP140, mediated by distinct mechanisms, coordinately contribute to the execution of stress response of the brain to Endoplasmic Reticulum (ER) stress, heat shock (HS) stress, oxidative stress and psychological/behavioral stress. In this review, we describe the roles of RIP140 in three brain cell types (neurons, microglia, and astrocytes) stressed by pharmacological agents or behavioral manipulation. These results demonstrate physiological integration of various functional roles of RIP140 in different brain cells to facilitate survival and recovery from stress. The results also suggest a potential, preventive and/or therapeutic strategy by targeting RIP140 in managing neurodegenerative diseases.

RIP140 in Stress Response of the Brain