title: Luteolin Reduces BACE1 Expression through NF-κB and through Estrogen Receptor Mediated Pathways in HEK293 and SH-SY5Y Cells.
abstract: Beta-secretase (BACE1) controls an essential step for the generation of amyloid- peptide (Aβ). As Aβ forms the principle pathologies in Alzheimer’s disease, lowering A production by inhibiting BACE1 is a plausible therapeutic approach. In the present study, we identified a natural polyphenol, luteolin, as a potent inhibitor of BACE1 transcription inhuman embryonic kidney 293 (HEK293) and human neuroblastoma (SH-SY5Y) cell lines. Luteolin is capable of suppressing the activation of BACE1 promoter by NF-κB signaling. We further characterized that luteolin interferes with NF-κB signaling by with both directly and indirectly disrupting p65 complex formation. In addition, we discovered that estrogen receptor mediates luteolin’s effect in inhibiting NF-κB signaling inhibiting and BACE1 transcription. Interestingly, the beneficial effects of luteolin may be attributed to selective activation profiles of luteolin to different estrogen receptor subtypes. Our study reports luteolin as a potent BACE1-inhibiting compound, providing useful information in understanding estrogen receptor- and NF-κB-mediated signaling and in regulating BACE1 expression.
authors.affiliation: College of Life Science, Wuhan University, Wuhan, Hubei, P.R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zheng
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Changhao
authors.initials: C
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Huang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D050882:CREB-Binding Protein / Q000378:metabolism; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D047468:Immunoprecipitation; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D009447:Neuroblastoma / Q000473:pathology; D011485:Protein Binding / Q000187:drug effects; D034622:RNA Interference / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D050882:CREB-Binding Protein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D047311:Luteolin