Nicotine Decreases Beta-Amyloid Through Regulating BACE1 Transcription in SH-EP1-alpha 4 beta 2 nAChR-APP695 Cells

作者：Nie, Hui Zhen; Li, Zuo Qing; Yan, Qi Xin; Wang, Ze Jian; Zhao, Wen Juan; Guo, Ling Chen; Yin, Ming^*

来源：Neurochemical Research, 2011, 36(5): 904-912.

DOI：10.1007/s11064-011-0420-7

• Alzheimer's disease
• Beta-amyloid
• BACE1
• nAChR

Alzheimer's disease (AD) is a neurodegenerative disorder that affects the elderly population. Deposition of beta-amyloid (A beta) 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) alpha 4 subunit and beta 2 subunit gene. In present study, we found that activation of alpha 4 beta 2 nAChR by nicotine and epibatidine decreased secreted A beta level in the cell line and hippocampal neurons, but had no effects on full-length APP695 and sAPP-alpha. Nicotine also decreases BACE1 and PSEN1 expression, as well as ERK1 and NF kappa B 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 alpha 4 beta 2 nAChR decreases A beta through regulating BACE1 transcription by ERK1-NF kappa B pathway. Additionally, analysis of BACE1 promoter activity by dual-luciferase reporter assay may be useful for drug screening as a high throughput method.

• 出版日期2011-5
• 单位上海交通大学