PMID- 25589732
OWN - NLM
STAT- MEDLINE
DCOM- 20160114
LR  - 20150626
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 45
IP  - 2
DP  - 2015
TI  - Luteolin Reduces BACE1 Expression through NF-kappaB and through Estrogen Receptor 
      Mediated Pathways in HEK293 and SH-SY5Y Cells.
PG  - 659-71
AB  - Beta-secretase (BACE1) controls an essential step for the generation of amyloid- 
      peptide (Abeta). As Abeta 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-kappaB signaling. We further characterized that 
      luteolin interferes with NF-kappaB 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-kappaB 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-kappaB-mediated signaling and in regulating BACE1 expression.
FAU - Zheng, Nan
AU  - Zheng N
AD  - College of Life Science, Wuhan University, Wuhan, Hubei, P.R. China.
FAU - Yuan, Peng
AU  - Yuan P
FAU - Li, Changhao
AU  - Li C
FAU - Wu, Jun
AU  - Wu J
FAU - Huang, Jian
AU  - Huang J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (BACE1 protein, human)
RN  - KUX1ZNC9J2 (Luteolin)
SB  - IM
MH  - Amyloid Precursor Protein Secretases/*metabolism
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Aspartic Acid Endopeptidases/*metabolism
MH  - CREB-Binding Protein/metabolism
MH  - Cell Line
MH  - Enzyme Inhibitors/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Immunoprecipitation
MH  - Luteolin/chemistry/*pharmacology
MH  - NF-kappa B/*metabolism
MH  - Neuroblastoma/pathology
MH  - Protein Binding/drug effects
MH  - RNA Interference/physiology
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Receptors, Estrogen/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Time Factors
MH  - Transfection
EDAT- 2015/01/16 06:00
MHDA- 2016/01/15 06:00
CRDT- 2015/01/16 06:00
PHST- 2015/01/16 06:00 [entrez]
PHST- 2015/01/16 06:00 [pubmed]
PHST- 2016/01/15 06:00 [medline]
AID - 771102H580866642 [pii]
AID - 10.3233/JAD-142517 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2015;45(2):659-71. doi: 10.3233/JAD-142517.