The clinical implication of β-arrestins-mediated signaling in memory and cognition.

Abstract

Arrestins, particularly β-arrestins, are multifunctional adapter proteins that regulate G protein-coupled receptors (GPCRs). These proteins are central to the desensitization, internalization, and downstream signaling of GPCRs, which are integrated into various physiological processes. Many studies have explored the extensive roles of β-arrestins in memory formation, consolidation, and psychoneurological disorders. The distribution of arrestins in the brain and their high expression in dopaminergic neurons and cortical pyramidal cells reveals their significant involvement in neural processes. Emerging evidence shows that β-arrestins contribute to memory modulation through receptor internalization and synaptic plasticity mechanisms. Notably, β-arrestins influence long-term potentiation (LTP) and long-term depression (LTD), essential processes in memory consolidation. In psychoneurological disorders, β-arrestins regulate neurotransmitter-receptor interactions, like dopaminergic pathways, which are implicated in mood and cognitive functions. The underlying role of β-arrestins in depression, schizophrenia, and autism spectrum disorder (ASD) highlights their therapeutic potential. β-Arrestin-biased ligands and the modulation of β-arrestin signaling pathways promise approaches for developing treatments with improved efficacy and reduced side effects. This review aims to underscore the diverse roles of β-arrestins in preserving neuronal function and their therapeutic potential in addressing memory-related and psychiatric disorders.