PMID- 24756894
OWN - NLM
STAT- MEDLINE
DCOM- 20150206
LR  - 20211021
IS  - 1550-7416 (Electronic)
IS  - 1550-7416 (Linking)
VI  - 16
IP  - 4
DP  - 2014 Jul
TI  - Curcumin inhibits the AKT/NF-kappaB signaling via CpG demethylation of the promoter 
      and restoration of NEP in the N2a cell line.
PG  - 649-57
LID - 10.1208/s12248-014-9605-8 [doi]
AB  - Curcumin (CUR), a non-toxic polyphenol from Curcuma longa, has been investigated 
      as a potential therapy with anti-inflammatory and anti-oxidative effects for 
      Alzheimer's disease (AD), which depicts features of chronic inflammatory 
      environment resulting in cellular death. However, it remains largely unknown 
      whether the anti-inflammatory effect of CUR in AD is associated with its property 
      of CpG demethylation, which is another function of CUR with the most research 
      interest during recent years. Neprilysin (NEP, EP24.11), a zinc-dependent 
      metallopeptidase expressed relatively low in the brain, is emerging as a potent 
      inhibitor of AKT/Protein Kinase B. In addition, hypermethylated promoter of NEP 
      has been reported to be associated with decreases in NEP expression. In the 
      present study, using bisulfite-sequencing PCR (BSP) assay, we showed that the CpG 
      sites in NEP gene were hypermethylated both in wild-type mouse neuroblastoma N2a 
      cells (N2a/wt) and N2a cells stably expressing human Swedish mutant amyloid 
      precursor protein (APP) (N2a/APPswe) associated with familial early onset AD. CUR 
      treatment induced restoration of NEP gene via CpG demethylation. This 
      CUR-mediated upregulation of NEP expression was also concomitant with the 
      inhibition of AKT, subsequent suppression of nuclear transcription factor-kappaB 
      (NF-kappaB) and its downstream pro-inflammatory targets including COX-2, iNOS in 
      N2a/APPswe cells. This study represents the first evidence on a link between CpG 
      demethylation effect on NEP and anti-inflammation ability of CUR that may provide 
      a novel mechanistic insight into the anti-inflammatory actions of CUR as well as 
      new basis for using CUR as a therapeutic intervention for AD.
FAU - Deng, Yushuang
AU  - Deng Y
AD  - Department of Neurology, The First Affiliated Hospital of Chongqing Medical 
      University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic 
      of China.
FAU - Lu, Xi
AU  - Lu X
FAU - Wang, Li
AU  - Wang L
FAU - Li, Tao
AU  - Li T
FAU - Ding, Yubin
AU  - Ding Y
FAU - Cao, Huimin
AU  - Cao H
FAU - Zhang, Yuping
AU  - Zhang Y
FAU - Guo, Xiuming
AU  - Guo X
FAU - Yu, Gang
AU  - Yu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140423
PL  - United States
TA  - AAPS J
JT  - The AAPS journal
JID - 101223209
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 3.4.24.11 (Neprilysin)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - Animals
MH  - Cell Line, Tumor
MH  - CpG Islands/*drug effects
MH  - Curcumin/*pharmacology
MH  - DNA Methylation/drug effects
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Mice
MH  - NF-kappa B/*drug effects
MH  - Neprilysin/*drug effects
MH  - Oncogene Protein v-akt/*antagonists & inhibitors
MH  - Signal Transduction/drug effects
PMC - PMC4070258
EDAT- 2014/04/24 06:00
MHDA- 2015/02/07 06:00
PMCR- 2015/04/23
CRDT- 2014/04/24 06:00
PHST- 2014/01/16 00:00 [received]
PHST- 2014/04/01 00:00 [accepted]
PHST- 2014/04/24 06:00 [entrez]
PHST- 2014/04/24 06:00 [pubmed]
PHST- 2015/02/07 06:00 [medline]
PHST- 2015/04/23 00:00 [pmc-release]
AID - 9605 [pii]
AID - 10.1208/s12248-014-9605-8 [doi]
PST - ppublish
SO  - AAPS J. 2014 Jul;16(4):649-57. doi: 10.1208/s12248-014-9605-8. Epub 2014 Apr 23.