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Type: Journal article
Title: Amyloid beta₁–-₄₂ (Aβ₄₂) up-regulates the expression of sortilin via the p75NTR/RhoA signaling pathway
Other Titles: Amyloid beta(1)--(42) (Abeta(42)) up-regulates the expression of sortilin via the p75NTR/RhoA signaling pathway
Author: Saadipour, K.
Yang, M.
Lim, Y.
Georgiou, K.
Sun, Y.
Keating, D.
Liu, J.
Wang, Y.
Gai, W.
Zhong, J.
Wang, Y.
Zhou, X.
Citation: Journal of Neurochemistry, 2013; 127(2):152-162
Publisher: Wiley
Issue Date: 2013
ISSN: 0022-3042
Statement of
Khalil Saadipour, Maio Yang, Yoon Lim, Kristen Georgiou, Ying Sun, Damien Keating, Jia Liu, Ye-Ran Wang, Wei-ping Gai, Jin-hua Zhong, Yan-Jiang Wang and Xin-fu Zhou
Abstract: Sortilin, a Golgi sorting protein and a member of the VPS10P family, is the co-receptor for proneurotrophins, regulates protein trafficking, targets proteins to lysosomes, and regulates low density lipoprotein metabolism. The aim of this study was to investigate the expression and regulation of sortilin in Alzheimer's disease (AD). A significantly increased level of sortilin was found in human AD brain and in the brains of 6-month-old swedish-amyloid precursor protein/PS1dE9 transgenic mice. Aβ₄₂ enhanced the protein and mRNA expression levels of sortilin in a dose- and time-dependent manner in SH-SY5Y cells, but had no effect on sorLA. In addition, proBDNF also significantly increased the protein and mRNA expression of sortilin in these cells. The recombinant extracellular domain of p75NTR (P75ECD-FC), or the antibody against the extracellular domain of p75NTR, blocked the up-regulation of sortilin induced by Amyloid-β protein (Aβ), suggesting that Aβ₄₂ increased the expression level of sortilin and mRNA in SH-SY5Y via the p75NTR receptor. Inhibition of ROCK, but not Jun N-terminal kinase, suppressed constitutive and Aβ₄₂-induced expression of sortilin. In conclusion, this study shows that sortilin expression is increased in the AD brain in human and mice and that Aβ₄₂ oligomer increases sortilin gene and protein expression through p75NTR and RhoA signaling pathways, suggesting a potential physiological interaction of Aβ₄₂ and sortilin in Alzheimer's disease.
Keywords: Alzheimer’s disease; Ab42; p75NTR; RhoA signaling pathway; sortilin
Rights: © 2013 International Society for Neurochemistry
RMID: 0030063162
DOI: 10.1111/jnc.12383
Grant ID:
Appears in Collections:Medicine publications

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