PMID- 23123787
OWN - NLM
STAT- MEDLINE
DCOM- 20130722
LR  - 20181202
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 531
IP  - 2
DP  - 2012 Dec 7
TI  - Chronic inhibition of glycogen synthase kinase-3 protects against 
      rotenone-induced cell death in human neuron-like cells by increasing BDNF 
      secretion.
PG  - 182-7
LID - S0304-3940(12)01414-0 [pii]
LID - 10.1016/j.neulet.2012.10.046 [doi]
AB  - Mitochondrial dysfunction is a common feature of many neurodegenerative 
      disorders. Likewise, activation of glycogen synthase kinase-3 (GSK-3) has been 
      proposed to play an important role in neurodegeneration. This multifunctional 
      protein kinase is involved in a number of cellular functions and we previously 
      showed that chronic inhibition of GSK-3 protects neuronal cells against 
      mitochondrial dysfunction-elicited cell death, through a mechanism involving 
      increased glucose metabolism and the translocation of hexokinase II (HKII) to 
      mitochondria. Here, we sought to gain deeper insight into the molecular basis of 
      this neuroprotection. We found that chronic inhibition of GSK-3, either 
      genetically or pharmacologically, elicited a marked increase in brain-derived 
      neurotrophic factor (BDNF) secretion, which in turn conferred resistance to 
      mitochondrial dysfunction through subcellular re-distribution of HKII. These 
      results define a molecular pathway through which chronic inhibition of GSK-3 may 
      protect neuronal cells from death. Moreover, they highlight the potential 
      benefits of enhanced neurotrophic factor secretion as a therapeutic approach to 
      treat neurodegenerative diseases.
CI  - Copyright (c) 2012 Elsevier Ireland Ltd. All rights reserved.
FAU - Gimenez-Cassina, Alfredo
AU  - Gimenez-Cassina A
AD  - Dept. de Biologia Molecular and Centro de Biologia Molecular Severo Ochoa 
      (UAM-CSIC) Universidad Autonoma de Madrid, 28049 Madrid, Spain. 
      Alfredo_gimenez-cassina@dfci.harvard.edu
FAU - Lim, Filip
AU  - Lim F
FAU - Diaz-Nido, Javier
AU  - Diaz-Nido J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121102
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Uncoupling Agents)
RN  - 03L9OT429T (Rotenone)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Death/physiology
MH  - Cell Line, Tumor
MH  - Fluorescent Antibody Technique
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Mitochondria/metabolism
MH  - Neurons/*metabolism
MH  - Rotenone/toxicity
MH  - Signal Transduction/*physiology
MH  - Uncoupling Agents/toxicity
EDAT- 2012/11/06 06:00
MHDA- 2013/07/23 06:00
CRDT- 2012/11/06 06:00
PHST- 2012/08/20 00:00 [received]
PHST- 2012/09/23 00:00 [revised]
PHST- 2012/10/09 00:00 [accepted]
PHST- 2012/11/06 06:00 [entrez]
PHST- 2012/11/06 06:00 [pubmed]
PHST- 2013/07/23 06:00 [medline]
AID - S0304-3940(12)01414-0 [pii]
AID - 10.1016/j.neulet.2012.10.046 [doi]
PST - ppublish
SO  - Neurosci Lett. 2012 Dec 7;531(2):182-7. doi: 10.1016/j.neulet.2012.10.046. Epub 
      2012 Nov 2.