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http://dx.doi.org/10.4014/jmb.1707.07003

Effects of Newly Synthesized Recombinant Human Amyloid-β Complexes and Poly-Amyloid-β Fibers on Cell Apoptosis and Cognitive Decline  

Park, Soojin (Graduate School of Medicine, Osaka University)
Huh, Jae-Won (National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Eom, Taekil (Subtropical/Tropical Organism Gene Bank, Jeju National University)
Park, Naeun (College of Pharmacy, Catholic University of Daegu)
Lee, Youngjeon (National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Ju-Sung (College of Applied Life Sciences, the Research Institute for Subtropical Agriculture and Biotechnology, Jeju National University)
Kim, Sun-Uk (National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Shim, Insop (Department of Science in Korean Medicine, Graduate School, College of Korean Medicine, Kyung Hee University)
Lee, Sang-Rae (National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Kim, Ekyune (College of Pharmacy, Catholic University of Daegu)
Publication Information
Journal of Microbiology and Biotechnology / v.27, no.11, 2017 , pp. 2044-2051 More about this Journal
Abstract
The main pathological hallmark of Alzheimer's disease is the deposition of amyloid-beta ($A{\beta}$) peptides in the brain. $A{\beta}$ has been widely used to mimic several aspects of Alzheimer's disease. However, several characteristics of amyloid-induced Alzheimer's disease pathology are not well established, especially in mice. The present study aimed to develop a new Alzheimer's disease model by investigating how $A{\beta}$ can be effectively aggregated using prokaryotes and eukaryotes. To express the $A{\beta}42$ complex in HEK293 cells, we cloned the $A{\beta}42$ region in a tandem repeat and incorporated the resulting construct into a eukaryotic expression vector. Following transfection into HEK293 cells via lipofection, cell viability assay and western blotting analysis revealed that exogenous $A{\beta}42$ can induce cell death and apoptosis. In addition, recombinant His-tagged $A{\beta}42$ was successfully expressed in Escherichia coli BL21 (DE3) and not only readily formed $A{\beta}$ complexes, but also inhibited the proliferation of SH-SY5Y cells and E. coli. For in vivo testing, recombinant His-tagged $A{\beta}42$ solution ($3{\mu}g/{\mu}l$ in $1{\times}PBS$ containing $1mM\;Ni^{2+}$) was injected stereotaxically into the left and right lateral ventricles of the brains of C57BL/6J mice (n = 8). Control mice were injected with $1{\times}PBS$ containing $1mM\;Ni^{2+}$ following the same procedure. Ten days after the sample injection, the Morris water maze test confirmed that exogenous $A{\beta}$ caused an increase in memory loss. These findings demonstrated that $Ni^{2+}$ is capable of complexing the 50-kDa amyloid and that intracerebroventricular injection of $A{\beta}42$ can lead to cognitive impairment, thereby providing improved Alzheimer's disease models.
Keywords
Amyloid-beta; recombinant protein; apoptosis; exogenous $A{\beta}42$ complex;
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