Alzheimer's disease (AD) is a neurodegenerative disorder that affects the elderly population. Deposition of beta-amyloid (Abeta) 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) alpha4 subunit and beta2 subunit gene. In present study, we found that activation of alpha4beta2 nAChR by nicotine and epibatidine decreased secreted Abeta 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 NFkappaB 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 alpha4beta2 nAChR decreases Abeta through regulating BACE1 transcription by ERK1-NFkappaB 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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