title: β-Arrestins as potential therapeutic targets for Alzheimer's disease.
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.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D019390:Arrestins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D000071557:beta-Arrestins