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Nicotine Decreases Beta-Amyloid Through Regulating BACE1 Transcription in SH-EP1-α4β2 nAChR-APP695 Cells

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Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects the elderly population. Deposition of beta-amyloid (Aβ) in the brain is a hallmark of AD pathology. In our previous study, we have constructed a cell line expressing human APP695 (hAPP695) in SH-EP1 cells stably transfected with human nicotinic receptor (nAChR) α4 subunit and β2 subunit gene. In present study, we found that activation of α4β2 nAChR by nicotine and epibatidine decreased secreted Aβ level in the cell line and hippocampal neurons, but had no effects on full-length APP695 and sAPP-α. Nicotine also decreases BACE1 and PSEN1 expression, as well as ERK1 and NFκB P65 subunit expression in the cell line. Furthermore, BACE1 promoter activity is, but PSEN1 not, decreased by nicotine in the cell line. All the results suggest that activation of α4β2 nAChR decreases Aβ through regulating BACE1 transcription by ERK1-NFκB pathway. Additionally, analysis of BACE1 promoter activity by dual-luciferase reporter assay may be useful for drug screening as a high throughput method.

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Acknowledgments

This work was supported by the grant from the Shanghai Committee of Science and Technology, China (Grant No. 08431900600), the grant from the National Comprehensive Technology Platforms for Innovative Drug R&D, China (2009ZX09301–007), the national natural science foundation of China (No. 30572179, 30672443), and financial support from China postdoctoral science foundation(20090450709). We thank Dr. Ronald J. Lukas for SH-EP1 cell line.

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Authors and Affiliations

  1. Laboratory of Neuropharmacology, School of Pharmacy, Shanghai Jiao Tong University, 200240, Shanghai, China

    Hui-Zhen Nie, Ze-Jian Wang, Wen-Juan Zhao, Ling-Chen Guo & Ming Yin

  2. Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, 200025, Shanghai, China

    Zuo-Qing Li

  3. Shenzhen Neptunus Bioengineering Holdings Co., LTD, 518057, Shenzhen, China

    Qi-Xin Yan

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  1. Hui-Zhen Nie
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  2. Zuo-Qing Li
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Correspondence to Ming Yin.

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Nie, HZ., Li, ZQ., Yan, QX. et al. Nicotine Decreases Beta-Amyloid Through Regulating BACE1 Transcription in SH-EP1-α4β2 nAChR-APP695 Cells. Neurochem Res 36, 904–912 (2011). https://doi.org/10.1007/s11064-011-0420-7

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  • DOI: https://doi.org/10.1007/s11064-011-0420-7

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