PMID- 26614345
OWN - NLM
STAT- MEDLINE
DCOM- 20170316
LR  - 20181113
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 59
IP  - 3
DP  - 2016 Jul
TI  - C6 Glioma-Secreted NGF and FGF2 Regulate Neuronal APP Processing Through 
      Up-Regulation of ADAM10 and Down-Regulation of BACE1, Respectively.
PG  - 334-42
LID - 10.1007/s12031-015-0690-7 [doi]
AB  - Excessive accumulation of amyloid-beta (Abeta) caused by cleavage of amyloid precursor 
      protein (APP) is thought to be the primary cause of Alzheimer's disease (AD). Two 
      key enzymes ADAM10 and BACE1 are involved in the initial cleavage of APP, 
      resulting in the onset of two pathways, the amyloidogenic pathway and the 
      non-amyloidogenic pathway, respectively. Altering APP metabolism towards the 
      non-amyloidogenic pathway is thought to reduce Abeta production. It has been 
      reported that, in vivo, exogenous neurotrophic factors make APP apt to entering 
      the non-amyloidogenic pathway. Since astrocytes secrete a battery of neurotrophic 
      factors, we investigated the role of astrocyte-derived factors in the dynamics of 
      Abeta generation in neural cells. Results show that C6 glioma cell-conditioned 
      medium (GCM), obtained from cultured astrocyte-derived C6 glioma cells, inhibit 
      Abeta1-42 production and shift APP processing towards the non-amyloidogenic pathway 
      in APPswe-HEK293 cells. Such effect is attributed to two key APP cleavage 
      enzymes, ADAM10 and BACE1. Two neurotrophic factors in the GCM, nerve growth 
      factor and fibroblast growth factor 2, are responsible for the up-regulation of 
      ADAM10 and down-regulation of BACE1, respectively. Our findings enhance our 
      understanding of the relationship between astrocytes and Abeta generation, 
      indicating that stimulation of astrocytic neurotrophic factors could slow AD 
      progression.
FAU - Xie, Huiping
AU  - Xie H
AD  - College of Life Sciences, Wuhan University, Room 5105, Wuhan, Hubei, 430072, 
      People's Republic of China.
FAU - Xiao, Zhimin
AU  - Xiao Z
AD  - College of Life Sciences, Wuhan University, Room 5105, Wuhan, Hubei, 430072, 
      People's Republic of China.
AD  - Sanofi, Cambridge, MA, 02142, USA.
FAU - Huang, Jian
AU  - Huang J
AD  - College of Life Sciences, Wuhan University, Room 5105, Wuhan, Hubei, 430072, 
      People's Republic of China. jianhuang@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20151127
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Membrane Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 9061-61-4 (Nerve Growth Factor)
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  - EC 3.4.24.81 (ADAM10 Protein)
RN  - EC 3.4.24.81 (ADAM10 protein, human)
SB  - IM
MH  - ADAM10 Protein/genetics/*metabolism
MH  - Amyloid Precursor Protein Secretases/genetics/*metabolism
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Aspartic Acid Endopeptidases/genetics/*metabolism
MH  - Astrocytes/metabolism
MH  - Cell Line, Tumor
MH  - Culture Media, Conditioned/pharmacology
MH  - Fibroblast Growth Factor 2/*metabolism/pharmacology
MH  - HEK293 Cells
MH  - Humans
MH  - Membrane Proteins/genetics/*metabolism
MH  - Nerve Growth Factor/*metabolism/pharmacology
MH  - Neurons/drug effects/*metabolism
MH  - Protein Processing, Post-Translational
OTO - NOTNLM
OT  - ADAM10
OT  - Astrocyte
OT  - BACE1
OT  - C6 glioma cell-conditioned medium
OT  - FGF2
OT  - NGF
EDAT- 2015/11/29 06:00
MHDA- 2017/03/17 06:00
CRDT- 2015/11/29 06:00
PHST- 2015/07/16 00:00 [received]
PHST- 2015/11/19 00:00 [accepted]
PHST- 2015/11/29 06:00 [entrez]
PHST- 2015/11/29 06:00 [pubmed]
PHST- 2017/03/17 06:00 [medline]
AID - 10.1007/s12031-015-0690-7 [pii]
AID - 10.1007/s12031-015-0690-7 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2016 Jul;59(3):334-42. doi: 10.1007/s12031-015-0690-7. Epub 2015 
      Nov 27.