Journal
MOLECULAR NEUROBIOLOGY
Volume 48, Issue 3, Pages 812-818Publisher
HUMANA PRESS INC
DOI: 10.1007/s12035-013-8469-8
Keywords
Alzheimer's disease; beta-arrestin; A beta; gamma-secretase; Therapy
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Funding
- National Natural Science Foundation of China [81000544, 81171209]
- Shandong Provincial Natural Science Foundation, China [ZR2010HQ004, ZR2011HZ001]
- Shandong Provincial Outstanding Medical Academic Professional Program
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beta-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 beta-arrestins levels were correlated with amyloid-beta peptide (A beta) pathology in brains of Alzheimer's disease (AD) patients and animal models. beta-arrestins could enhance the activity of gamma-secretase via interacting with anterior pharynx defective 1 subunit, which increased A beta production and contributed to the pathogenesis of AD. In addition, A beta-induced internalization of beta 2-adrenergic receptor internalization and loss of dendritic spine in neurons were proven to be mediated by beta-arrestins, further establishing their pathogenic role in AD. More importantly, deletion of beta-arrestins markedly attenuated AD pathology, without causing any gross abnormality. Here, we review the evidence about the roles of beta-arrestins in the progression of AD. In addition, the established and postulated mechanisms by which beta-arrestins mediated in AD pathogenesis are also discussed. Based on the role of beta-arrestins in AD pathogenesis, genetically or pharmacologically targeting beta-arrestins might provide new opportunities for AD treatment.
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