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Targeting β-Arrestins in the Treatment of Psychiatric and Neurological Disorders

Abstract

Therapies for psychiatric and neurological disorders have been in the development and refinement process for the past 5 decades. Yet, most of these therapies lack optimal therapeutic efficacy and have multiple debilitating side effects. Recent advances in understanding the pathophysiological processes of psychiatric and neurological disorders have revealed an important role for β-arrestins, which are important regulators of G-protein-coupled receptor (GPCR) function, including desensitization and intracellular signaling. These findings have pushed β-arrestins to the forefront as potential therapeutic targets. Here, we highlight current knowledge on β-arrestin functions in certain psychiatric and neurological disorders (schizophrenia, Parkinson’s disease, and substance abuse disorders), and how this has been leveraged to develop new therapeutic strategies. Furthermore, we discuss the obstacles impacting the field of β-arrestin-based therapeutic development and future approaches that might help advance strategies to develop optimal β-arrestin-based therapies.

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Correspondence to Nikhil M. Urs.

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We would like to thank the Michael J. Fox Foundation (MJFF) and the Brain and Behavior Research Foundation (BBRF) (formally, the National Alliance for Research on Schizophrenia and Depression [NARSAD]) for partially funding our research program at the University of Florida.

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SSH and NMU wrote the manuscript.

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Harris, S.S., Urs, N.M. Targeting β-Arrestins in the Treatment of Psychiatric and Neurological Disorders. CNS Drugs 35, 253–264 (2021). https://doi.org/10.1007/s40263-021-00796-y

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