PMID- 25017047
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20180712
IS  - 1879-1220 (Electronic)
IS  - 0960-0760 (Linking)
VI  - 144 Pt B
DP  - 2014 Oct
TI  - Estrogen receptor alpha promotes non-amyloidogenic processing of platelet amyloid 
      precursor protein via the MAPK/ERK pathway.
PG  - 280-5
LID - S0960-0760(14)00127-7 [pii]
LID - 10.1016/j.jsbmb.2014.06.010 [doi]
AB  - Deposition of amyloid beta peptide (Abeta), a proteolytic product of amyloid precursor 
      protein (APP), in senile plaques and in the walls of cerebral blood vessels is a 
      hallmark of Alzheimer's disease (AD). Platelets contain high levels of APP and Abeta 
      and may contribute to amyloid deposits seen in AD. However, the biochemical 
      mechanism(s) involved in the regulation of platelet APP metabolism are largely 
      unknown. The estrogen receptor alpha (ERalpha) is found to be expressed in platelets. It 
      has not been elucidated whether ERalpha-mediated non-genomic signaling intervenes 
      with platelet APP processing. Using ERalpha knock-out (alpha-ERKO) mice and wild type 
      (WT) littermates, the present study demonstrated that ERalpha-specific agonist 
      propylpyrazole triol (PPT) promoted non-amyloidogenic processing of platelet APP 
      via the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated 
      kinase (ERK) pathway. The underlying basis involves direct association of 
      activated ERK with a disintegrin and metalloprotease domain 17 (ADAM17, an 
      alpha-secretase candidate) and ERK-dependent threonine phosphorylation of ADAM17. 
      These results suggest that selective modulation of ERalpha in peripheral target 
      tissues may serve as an anti-amyloidogenic strategy for AD and other 
      amyloidogenic diseases.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Shi, Chun
AU  - Shi C
AD  - Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, 
      China. Electronic address: sallyshi431@126.com.
FAU - Zhu, XiaoMing
AU  - Zhu X
AD  - Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, 
      China.
FAU - Wang, Jisheng
AU  - Wang J
AD  - Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, 
      China.
FAU - Long, Dahong
AU  - Long D
AD  - Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 510182, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140710
PL  - England
TA  - J Steroid Biochem Mol Biol
JT  - The Journal of steroid biochemistry and molecular biology
JID - 9015483
RN  - 0 (APP protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Phenols)
RN  - 0 (Pyrazoles)
RN  - 0T83Y6JZPF (4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Blood Platelets/drug effects/*metabolism
MH  - Estrogen Receptor alpha/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Female
MH  - *MAP Kinase Signaling System
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Phenols
MH  - Pyrazoles/pharmacology
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid beta protein
OT  - Estrogen receptor alpha
OT  - Platelet
EDAT- 2014/07/16 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/07/15 06:00
PHST- 2014/04/12 00:00 [received]
PHST- 2014/06/14 00:00 [revised]
PHST- 2014/06/21 00:00 [accepted]
PHST- 2014/07/15 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - S0960-0760(14)00127-7 [pii]
AID - 10.1016/j.jsbmb.2014.06.010 [doi]
PST - ppublish
SO  - J Steroid Biochem Mol Biol. 2014 Oct;144 Pt B:280-5. doi: 
      10.1016/j.jsbmb.2014.06.010. Epub 2014 Jul 10.