Department of Pharmacology and Therapeutics, University of Florida, 1200 Newell Dr, ARB-R5-140, Gainesville, FL, 32610, USA.
CNS Drugs. 2021 Mar;35(3):253-264. doi: 10.1007/s40263-021-00796-y. Epub 2021 Mar 2.
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.
过去 50 年来，精神和神经疾病的治疗方法一直在不断发展和完善。然而，这些疗法大多缺乏最佳疗效，并伴有多种使人虚弱的副作用。最近对精神和神经疾病病理生理过程的深入了解揭示了β-arrestin 的重要作用，β-arrestin 是 G 蛋白偶联受体 (GPCR) 功能的重要调节剂，包括脱敏和细胞内信号转导。这些发现将β-arrestin 推向了作为潜在治疗靶点的前沿。在这里，我们重点介绍了β-arrestin 在某些精神和神经疾病（精神分裂症、帕金森病和物质滥用障碍）中的功能的最新知识，以及如何利用这些知识来开发新的治疗策略。此外，我们还讨论了影响β-arrestin 为基础的治疗开发领域的障碍，以及未来可能有助于推进开发最佳β-arrestin 为基础的治疗策略的方法。
