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β-Arrestins as Potential Therapeutic Targets for Alzheimer’s Disease

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Abstract

β-arrestins represent a small family of G protein-coupled receptors (GPCRs) regulators, which provide modulating effects by facilitating desensitization and internalization of GPCRs as well as initiating their own signalings. Recent reports have demonstrated that β-arrestins levels were correlated with amyloid-β peptide (Aβ) pathology in brains of Alzheimer’s disease (AD) patients and animal models. β-arrestins could enhance the activity of γ-secretase via interacting with anterior pharynx defective 1 subunit, which increased Aβ production and contributed to the pathogenesis of AD. In addition, Aβ-induced internalization of β2-adrenergic receptor internalization and loss of dendritic spine in neurons were proven to be mediated by β-arrestins, further establishing their pathogenic role in AD. More importantly, deletion of β-arrestins markedly attenuated AD pathology, without causing any gross abnormality. Here, we review the evidence about the roles of β-arrestins in the progression of AD. In addition, the established and postulated mechanisms by which β-arrestins mediated in AD pathogenesis are also discussed. Based on the role of β-arrestins in AD pathogenesis, genetically or pharmacologically targeting β-arrestins might provide new opportunities for AD treatment.

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Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (81000544, 81171209), the Shandong Provincial Natural Science Foundation, China (ZR2010HQ004, ZR2011HZ001), and the Shandong Provincial Outstanding Medical Academic Professional Program.

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We declare that we have no conflicts of interest.

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Authors and Affiliations

  1. Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China

    Teng Jiang, Jin-Tai Yu, Xi-Chen Zhu & Lan Tan

  2. Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China

    Jin-Tai Yu & Lan Tan

  3. College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China

    Jin-Tai Yu, Meng-Shan Tan & Lan Tan

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  1. Teng Jiang
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Jiang, T., Yu, JT., Tan, MS. et al. β-Arrestins as Potential Therapeutic Targets for Alzheimer’s Disease. Mol Neurobiol 48, 812–818 (2013). https://doi.org/10.1007/s12035-013-8469-8

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