PMID- 21630010
OWN - NLM
STAT- MEDLINE
DCOM- 20120208
LR  - 20220208
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 36
IP  - 10
DP  - 2011 Oct
TI  - Activation of liver X receptor decreases BACE1 expression and activity by 
      reducing membrane cholesterol levels.
PG  - 1910-21
LID - 10.1007/s11064-011-0513-3 [doi]
AB  - The synthetic Liver X receptor (LXR) activator T0901317 has been reported to 
      exert neuroprotective effect in Alzheimer's disease, but the relationship between 
      LXR activation and beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1) 
      remains uncertain. This study investigated the effect of T0901317 on membrane 
      cholesterol levels, BACE1 expression and activity. We found that T0901317 
      decreased membrane cholesterol levels, reduced BACE1 expression and activity as 
      well as beta-secretase cleaved C-terminal fragment (beta-CTF) levels in vivo and in 
      vitro. Meanwhile, the expression of ATP-binding membrane cassette transport 
      protein A1 (ABCA1) enhanced. Additionally, inhibition of ABCA1 abrogated the 
      effects of T0901317 on membrane cholesterol levels and beta-secretase activity. 
      Moreover, addition of LXR antagonist reversed the effect of T0901317 on ABCA1 
      mRNA expression, membrane cholesterol levels and beta-secretase activity. Our 
      results suggest that activation of LXR may decrease BACE1 expression and activity 
      through a pathway associated with ABCA1-mediated reduction in membrane 
      cholesterol levels.
FAU - Cui, Weigang
AU  - Cui W
AD  - Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan 
      University, 200032 Shanghai, China.
FAU - Sun, Yan
AU  - Sun Y
FAU - Wang, Zhongping
AU  - Wang Z
FAU - Xu, Chongchong
AU  - Xu C
FAU - Xu, Li
AU  - Xu L
FAU - Wang, Fei
AU  - Wang F
FAU - Chen, Zulin
AU  - Chen Z
FAU - Peng, Yuwen
AU  - Peng Y
FAU - Li, Ruixi
AU  - Li R
LA  - eng
PT  - Journal Article
DEP - 20110601
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Liver X Receptors)
RN  - 0 (Oligopeptides)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Peptide Fragments)
RN  - 0 (Presenilin-1)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.23.- (Aspartic Acid Endopeptidases)
RN  - EC 3.4.23.46 (Bace1 protein, mouse)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/antagonists & inhibitors/genetics/metabolism
MH  - Amyloid Precursor Protein Secretases/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Apolipoproteins E/genetics/metabolism
MH  - Aspartic Acid Endopeptidases/antagonists & inhibitors/genetics/*metabolism
MH  - Cell Membrane/*chemistry/*drug effects/*metabolism
MH  - Cells, Cultured
MH  - Cholesterol/*metabolism
MH  - Gene Expression
MH  - Hippocampus/cytology
MH  - Humans
MH  - Hydrocarbons, Fluorinated/*pharmacology
MH  - Liver X Receptors
MH  - Mice
MH  - Mice, Transgenic
MH  - Neurons/cytology/metabolism
MH  - Oligopeptides/genetics/metabolism
MH  - Orphan Nuclear Receptors/genetics/*metabolism
MH  - Peptide Fragments/metabolism
MH  - Presenilin-1/genetics/metabolism
MH  - Sulfonamides/*pharmacology
EDAT- 2011/06/02 06:00
MHDA- 2012/02/09 06:00
CRDT- 2011/06/02 06:00
PHST- 2011/05/14 00:00 [accepted]
PHST- 2011/06/02 06:00 [entrez]
PHST- 2011/06/02 06:00 [pubmed]
PHST- 2012/02/09 06:00 [medline]
AID - 10.1007/s11064-011-0513-3 [doi]
PST - ppublish
SO  - Neurochem Res. 2011 Oct;36(10):1910-21. doi: 10.1007/s11064-011-0513-3. Epub 2011 
      Jun 1.