title: Nicotine decreases beta-amyloid through regulating BACE1 transcription in SH-EP1-α4β2 nAChR-APP695 cells.
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.
authors.affiliation: Laboratory of Neuropharmacology, School of Pharmacy, Shanghai Jiao Tong University, 200240 Shanghai, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Nie
authors.forename: Zuo-Qing
authors.initials: ZQ
authors.lastname: Li
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Yan
authors.forename: Ze-Jian
authors.initials: ZJ
authors.lastname: Wang
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Zhao
authors.forename: Ling-Chen
authors.initials: LC
authors.lastname: Guo
authors.forename: Ming
authors.initials: M
authors.lastname: Yin
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D009538:Nicotine / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011978:Receptors, Nicotinic / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D011978:Receptors, Nicotinic; D009538:Nicotine; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human