Title |
β-Arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology
|
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Published in |
Cell Research, December 2012
|
DOI | 10.1038/cr.2012.167 |
Pubmed ID | |
Authors |
Xiaosong Liu, Xiaohui Zhao, Xianglu Zeng, Koen Bossers, Dick F Swaab, Jian Zhao, Gang Pei |
Abstract |
Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease in which the γ-secretase-mediated amyloid-β (Aβ) pathology plays an important role. We found that a multifunctional protein, β-arrestin1, facilitated the formation of NCT/APH-1 (anterior pharynx-defective phenotype 1) precomplex and mature γ-secretase complex through its functional interaction with APH-1. Deficiency of β-arrestin1 or inhibition of binding of β-arrestin1 with APH-1 by small peptides reduced Aβ production without affecting Notch processing. Genetic ablation of β-arrestin1 diminished Aβ pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of β-arrestin1 was upregulated and correlated well with neuropathological severity and senile Aβ plaques. Thus, our study identifies a regulatory mechanism underlying both γ-secretase assembly and AD pathogenesis, and indicates that specific reduction of Aβ pathology can be achieved by regulation of the γ-secretase assembly. |
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Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | 2% |
Unknown | 46 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Master | 8 | 17% |
Student > Ph. D. Student | 8 | 17% |
Researcher | 6 | 13% |
Student > Bachelor | 5 | 11% |
Student > Doctoral Student | 4 | 9% |
Other | 8 | 17% |
Unknown | 8 | 17% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 9 | 19% |
Agricultural and Biological Sciences | 8 | 17% |
Neuroscience | 7 | 15% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 9% |
Chemistry | 3 | 6% |
Other | 7 | 15% |
Unknown | 9 | 19% |