PMID- 20603607
OWN - NLM
STAT- MEDLINE
DCOM- 20111123
LR  - 20211203
IS  - 1551-4005 (Electronic)
IS  - 1538-4101 (Print)
IS  - 1551-4005 (Linking)
VI  - 9
IP  - 12
DP  - 2010 Jun 15
TI  - Regulation of cell death and epileptogenesis by the mammalian target of rapamycin 
      (mTOR): a double-edged sword?
PG  - 2281-5
AB  - Identification of cell signaling mechanisms mediating seizure-related neuronal 
      death and epileptogenesis is important for developing more effective therapies 
      for epilepsy. The mammalian target of rapamycin (mTOR) pathway has recently been 
      implicated in regulating neuronal death and epileptogenesis in rodent models of 
      epilepsy. In particular, kainate-induced status epilepticus causes abnormal 
      activation of the mTOR pathway, and the mTOR inhibitor, rapamycin, can decrease 
      the development of neuronal death and chronic seizures in the kainate model. 
      Here, we discuss the significance of these findings and extend them further by 
      identifying upstream signaling pathways through which kainate status epilepticus 
      activates the mTOR pathway and by demonstrating limited situations where 
      rapamycin may paradoxically increase mTOR activation and worsen neuronal death in 
      the kainate model. Thus, the regulation of seizure-induced neuronal death and 
      epileptogenesis by mTOR is complex and may have dual, opposing effects depending 
      on the physiological and pathological context. Overall, these findings have 
      important implications for designing potential neuroprotective and 
      antiepileptogenic therapies that modulate the mTOR pathway.
FAU - Zeng, Ling-Hui
AU  - Zeng LH
AD  - Department of Pharmacy, Zhejiang University City College, Hangzhou, Zhejiang, 
      China.
FAU - McDaniel, Sharon
AU  - McDaniel S
FAU - Rensing, Nicholas R
AU  - Rensing NR
FAU - Wong, Michael
AU  - Wong M
LA  - eng
GR  - K02 NS045583/NS/NINDS NIH HHS/United States
GR  - R01 NS056872/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100615
PL  - United States
TA  - Cell Cycle
JT  - Cell cycle (Georgetown, Tex.)
JID - 101137841
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Kainic Acid)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Death/drug effects
MH  - Epilepsy/*metabolism/pathology
MH  - Mice
MH  - Neurons/metabolism/pathology
MH  - Neuroprotective Agents/pharmacology
MH  - Phosphatidylinositol 3-Kinase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Receptors, Kainic Acid/metabolism
MH  - Signal Transduction/drug effects
MH  - Status Epilepticus/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3934644
MID - NIHMS544521
EDAT- 2010/07/07 06:00
MHDA- 2011/12/13 00:00
PMCR- 2014/02/25
CRDT- 2010/07/07 06:00
PHST- 2010/07/07 06:00 [entrez]
PHST- 2010/07/07 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2014/02/25 00:00 [pmc-release]
AID - 11866 [pii]
AID - 10.4161/cc.9.12.11866 [doi]
PST - ppublish
SO  - Cell Cycle. 2010 Jun 15;9(12):2281-5. doi: 10.4161/cc.9.12.11866. Epub 2010 Jun 
      15.