PMID- 24161275
OWN - NLM
STAT- MEDLINE
DCOM- 20140827
LR  - 20161125
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 256
DP  - 2014 Jan 3
TI  - Human apolipoprotein E4 modulates the expression of Pin1, Sirtuin 1, and 
      Presenilin 1 in brain regions of targeted replacement apoE mice.
PG  - 360-9
LID - S0306-4522(13)00861-0 [pii]
LID - 10.1016/j.neuroscience.2013.10.017 [doi]
AB  - The apolipoprotein E4 (apoE4) allele is consistently associated with increased 
      risk for Alzheimer's disease (AD). We investigated the molecular mechanism of 
      this susceptibility by analyzing the levels of genes involved in AD pathogenesis 
      in transgenic mice expressing human apoE3 or apoE4 isoforms. mRNA and protein 
      levels of Pin1, Sirtuin 1 (Sirt1), Presenilin 1 (PS1), and pro-Brain-derived 
      Neurotrophic Factor (BDNF) were analyzed in brain regions affected by 
      neuropathological changes in AD. Pin1 mRNA was significantly higher in the 
      hippocampus of apoE4 mice than in apoE3 controls, whereas lower expression was 
      detected in the entorhinal and parietal cortices. Reduced Pin1 levels may 
      increase neurofibrillary degeneration and amyloidogenic processes, while 
      compensatory mechanisms may take place in the hippocampus to balance spatial 
      memory deficits. Sirt1 levels were significantly reduced in the frontal cortex of 
      apoE4 mice. Sirt1 reduction may hinder its protective role against the formation 
      of plaques and tangles and diminish its anti-inflammatory actions. Sirt1 decrease 
      may also play a role in apoE4-associated memory impairments. Moreover, in apoE4 
      mice PS1 mRNA levels were lower in the frontal cortex. Lower PS1 expression may 
      hamper gamma-secretase function, thus affecting amyloid precursor protein processing. 
      Pro-BDNF mRNA levels did not differ between apoE3 and apoE4 mice in any region 
      analyzed. This study showed dysregulated expression of Pin1, Sirt1, and PS1 genes 
      in different cerebral areas of apoE4 mice, suggesting that these changes may play 
      a role in the mechanism of AD vulnerability.
CI  - Copyright (c) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Lattanzio, F
AU  - Lattanzio F
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy.
FAU - Carboni, L
AU  - Carboni L
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy. Electronic address: 
      lucia.carboni4@unibo.it.
FAU - Carretta, D
AU  - Carretta D
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy.
FAU - Rimondini, R
AU  - Rimondini R
AD  - Department of Medical and Clinical Science, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy.
FAU - Candeletti, S
AU  - Candeletti S
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy.
FAU - Romualdi, P
AU  - Romualdi P
AD  - Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of 
      Bologna, via Irnerio 48, 40126 Bologna, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131023
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Apolipoprotein E4)
RN  - 0 (NIMA-Interacting Peptidylprolyl Isomerase)
RN  - 0 (Presenilin-1)
RN  - 0 (RNA, Messenger)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - EC 5.2.1.8 (PIN1 protein, human)
RN  - EC 5.2.1.8 (Peptidylprolyl Isomerase)
RN  - EC 5.2.1.8 (Pin1 protein, mouse)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Apolipoprotein E4/genetics/*metabolism
MH  - Brain/*metabolism
MH  - Gene Expression Regulation/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - NIMA-Interacting Peptidylprolyl Isomerase
MH  - Peptidylprolyl Isomerase/genetics/*metabolism
MH  - Presenilin-1/genetics/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Sirtuin 1/genetics/*metabolism
OTO - NOTNLM
OT  - AD
OT  - APP
OT  - Alzheimer's disease
OT  - Abeta
OT  - BDNF
OT  - Brain-derived Neurotrophic Factor
OT  - DDCt
OT  - Delta-Delta Ct
OT  - EDTA
OT  - Forkhead box protein O
OT  - FoxO
OT  - LDL
OT  - NF-kappaB
OT  - NT
OT  - Nuclear factor kappa B
OT  - PS1
OT  - Pin1
OT  - Presenilin 1
OT  - RT-qPCR
OT  - S.E.M.
OT  - Sirt1
OT  - Sirtuin 1
OT  - amyloid beta peptide
OT  - amyloid precursor protein
OT  - apoE
OT  - apoE TR mice
OT  - apolipoprotein E
OT  - apoliporpotein E
OT  - ethylenediaminetetraacetic acid
OT  - human apoE3- and apoE4-targeted replacement mice
OT  - low-density lipoprotein
OT  - neurofibrillary tangles
OT  - reverse transcription quantitative real-time polymerase chain reaction
OT  - standard error of the mean
EDAT- 2013/10/29 06:00
MHDA- 2014/08/29 06:00
CRDT- 2013/10/29 06:00
PHST- 2013/09/11 00:00 [received]
PHST- 2013/10/09 00:00 [accepted]
PHST- 2013/10/29 06:00 [entrez]
PHST- 2013/10/29 06:00 [pubmed]
PHST- 2014/08/29 06:00 [medline]
AID - S0306-4522(13)00861-0 [pii]
AID - 10.1016/j.neuroscience.2013.10.017 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Jan 3;256:360-9. doi: 10.1016/j.neuroscience.2013.10.017. Epub 
      2013 Oct 23.