Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro.
Low-Density Lipoprotein Receptor-Related Protein-1 (LRP1) C4408R Mutant Promotes Amyloid Precursor Protein (APP) α-Cleavage in Vitro.
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DOI：
10.1007/s12017-017-8446-x
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发表时间：
2017-09
影响因子：
3.5
通讯作者：
Tan J
中科院分区：
文献类型：
--
作者：
Hou H;Habib A;Zi D;Tian K;Tian J;Giunta B;Sawmiller D;Tan J
Previous studies have demonstrated that the low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) plays conflicting roles in Alzheimer’s disease (AD) pathogenesis, clearing β-amyloid (Aβ) from the brain while also enhancing APP endocytosis and resultant amyloidogenic processing. We have recently discovered that coexpression of mutant LRP1 C-terminal domain (LRP1-CT C4408R) with Swedish mutant amyloid precursor protein (APPswe) in Chinese hamster ovary (CHO) cells decreases Aβ production, while also increasing sAPPα and APP α-C-terminal fragment (α-CTF), compared with CHO cells expressing APPswe alone. Surprisingly, the location of this mutation on LRP1 corresponded with the α-secretase cleavage site of APP. Further experimentation confirmed that in CHO cells expressing APPswe or wild-type APP (APPwt), coexpression of LRP1-CT C4408R decreases Aβ and increases sAPPα and α-CTF compared with coexpression of wild-type LRP1-CT. In addition, LRP1-CT C4408R enhanced the unglycosylated form of LRP1-CT and reduced APP endocytosis as determined by flow cytometry. This finding identifies a point mutation in LRP1 which slows LRP1-CT-mediated APP endocytosis and amyoloidogenic processing, while enhancing APP α-secretase cleavage, thus demonstrating a potential novel target for slowing AD pathogenesis.
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DOI：
10.1523/jneurosci.6473-11.2012
发表时间：
2012-08-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lefort R;Pozueta J;Shelanski M
通讯作者：
Shelanski M
影响因子：
3.7
作者：
Dieckmann M;Dietrich MF;Herz J
通讯作者：
Herz J
影响因子：
4.7
作者：
Deng J;Habib A;Obregon DF;Barger SW;Giunta B;Wang YJ;Hou H;Sawmiller D;Tan J
通讯作者：
Tan J
影响因子：
21.3
作者：
Bell, Robert D.;Deane, Rashid;Chow, Nienwen;Long, Xiaochun;Sagare, Abhay;Singh, Itender;Streb, Jeffrey W.;Guo, Huang;Rubio, Anna;Van Nostrand, William;Miano, Joseph M.;Zlokovic, Berislav V.
通讯作者：
Zlokovic, Berislav V.
影响因子：
5.8
作者：
Boucher P;Herz J
通讯作者：
Herz J