The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.
The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.
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DOI：
10.1038/s12276-023-01144-4
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发表时间：
2024-02
影响因子：
12.8
通讯作者：
Woo, Jung-A A.
中科院分区：
文献类型：
--
作者：
Kee, Teresa R.;Khan, Sophia A.;Neidhart, Maya B.;Masters, Brianna M.;Zhao, Victoria K.;Kim, Yenna K.;McGill Percy, Kyle C.;Woo, Jung-A A.
抑制蛋白是调节G蛋白偶联受体（GPCR）脱敏、信号传导和内化的多功能蛋白质。arrestin家族由四种亚型组成：visual arrestin 1、β-arrestin 1、β-arrestin 2和visual arrestin-4。最近的研究揭示了β-arrestins除了GPCR信号传导之外的多功能作用，包括支架和衔接子功能，以及与非GPCR受体的物理相互作用。越来越多的证据表明，β-arrestins参与多种神经退行性疾病的发病机制，包括阿尔茨海默病（AD）、额颞叶痴呆（FTD）和帕金森病（PD）。β-抑制蛋白与γ-分泌酶物理相互作用，导致AD中淀粉样蛋白β的产生和积累增加。此外，β-抑制蛋白寡聚体抑制自噬货物受体p62/SQSTM 1，导致FTD中tau蓄积和聚集。在PD中，β-arrestins在死后脑组织和MPTP模型中上调，β2AR调节SNCA基因表达。本文就β-arrestin 1和β-arrestin 2的研究进展作一综述，并阐述其生理功能及其在神经退行性疾病中的作用。β-arrestins的多方面作用及其在神经退行性疾病中的参与表明它们可能作为有希望的治疗靶点。阿尔茨海默病、帕金森病、额颞叶痴呆和肌萎缩侧索硬化症是影响全世界数百万人的神经退行性疾病。最近的研究已经确定了这些疾病与β-抑制蛋白（一种与G蛋白偶联受体（GPCR）相互作用的调节蛋白）之间的显著关联。GPCR在许多生物过程中起着至关重要的作用，并且是许多药物治疗的焦点。这篇综述文章提供了一个全面的总结β-arrestins的既定功能，并强调了最近的发现β-arrestins与神经退行性疾病。此外，它通过以避免破坏其与GPCR的重要相互作用的方式靶向β-抑制蛋白来探索新的治疗途径。研究人员认为，这种策略可以为这些使人衰弱的疾病带来更有效和更具体的治疗方法。
Arrestins are multifunctional proteins that regulate G-protein-coupled receptor (GPCR) desensitization, signaling, and internalization. The arrestin family consists of four subtypes: visual arrestin1, β-arrestin1, β-arrestin2, and visual arrestin-4. Recent studies have revealed the multifunctional roles of β-arrestins beyond GPCR signaling, including scaffolding and adapter functions, and physically interacting with non-GPCR receptors. Increasing evidence suggests that β-arrestins are involved in the pathogenesis of a variety of neurodegenerative diseases, including Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease (PD). β-arrestins physically interact with γ-secretase, leading to increased production and accumulation of amyloid-beta in AD. Furthermore, β-arrestin oligomers inhibit the autophagy cargo receptor p62/SQSTM1, resulting in tau accumulation and aggregation in FTD. In PD, β-arrestins are upregulated in postmortem brain tissue and an MPTP model, and the β2AR regulates SNCA gene expression. In this review, we aim to provide an overview of β-arrestin1 and β-arrestin2, and describe their physiological functions and roles in neurodegenerative diseases. The multifaceted roles of β-arrestins and their involvement in neurodegenerative diseases suggest that they may serve as promising therapeutic targets. Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, and amyotrophic lateral sclerosis are neurodegenerative diseases impacting millions worldwide. Recent research has identified a significant association between these diseases and beta-arrestin, a regulatory protein that interacts with G-protein-coupled receptors (GPCRs). GPCRs play crucial roles in numerous biological processes and are the focus of many drug therapies. This review article provides a comprehensive summary of the established functions of beta-arrestins and underscores recent findings linking beta-arrestins to neurodegenerative diseases. Furthermore, it explores novel therapeutic avenues by targeting beta-arrestins in a manner that avoids disrupting their vital interactions with GPCRs. Researchers believe this strategy could lead to more efficient and specific treatments for these debilitating diseases.
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影响因子：
3.2
作者：
Bargiotas P;Konitsiotis S
通讯作者：
Konitsiotis S
影响因子：
6.1
作者：
Bezard, E;Gross, CE;Gurevich, EV
通讯作者：
Gurevich, EV
DOI：
10.1073/pnas.0705550104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Boularan, Cedric;Scott, Mark G. H.;Marullo, Stefano
通讯作者：
Marullo, Stefano
影响因子：
--
作者：
Alvarez-Erviti, Lydia;Rodriguez-Oroz, Maria C.;Schapira, Anthony H. V.
通讯作者：
Schapira, Anthony H. V.
DOI：
10.1073/pnas.83.9.2797
发表时间：
1986-05-01
影响因子：
11.1
作者：
BENOVIC, JL;STRASSER, RH;LEFKOWITZ, RJ
通讯作者：
LEFKOWITZ, RJ