PMID- 21354266
OWN - NLM
STAT- MEDLINE
DCOM- 20120302
LR  - 20211203
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 497
IP  - 3
DP  - 2011 Jun 27
TI  - Therapeutic role of mammalian target of rapamycin (mTOR) inhibition in preventing 
      epileptogenesis.
PG  - 231-9
LID - 10.1016/j.neulet.2011.02.037 [doi]
AB  - Traditionally, medical therapy for epilepsy has aimed to suppress seizure 
      activity, but has been unable to alter the progression of the underlying disease. 
      Recent advances in our understanding of mechanisms of epileptogenesis open the 
      door for the development of new therapies which prevent the pathogenic changes in 
      the brain that predispose to spontaneous seizures. In particular, the mammalian 
      target of rapamycin (mTOR) signaling pathway has recently garnered interest as an 
      important regulator of cellular changes involved in epileptogenesis, and mTOR 
      inhibitors have generated excitement as potential antiepileptogenic agents. mTOR 
      hyperactivation occurs in tuberous sclerosis complex (TSC), a common genetic 
      cause of epilepsy, as a result of genetic mutations in upstream regulatory 
      molecules. mTOR inhibition prevents epilepsy and brain pathology in animal models 
      of TSC. mTOR dysregulation has also been demonstrated in a variety of other 
      genetic and acquired epilepsies, including brain tumors, focal cortical 
      dysplasias, and animal models of brain injury due to status epilepticus or 
      trauma. Indeed, mTOR inhibitors appear to possess antiepileptogenic properties in 
      animal models of acquired epilepsy as well. Thus, mTOR dysregulation may 
      represent a final common pathway in epilepsies of various causes. Therefore, mTOR 
      inhibition is an exciting potential antiepileptogenic strategy with broad 
      applications for epilepsy and could be involved in a number of treatment 
      modalities, including the ketogenic diet. Further research is necessary to 
      determine the clinical utility of rapamycin and other mTOR inhibitors for 
      antiepileptogenesis, and to devise new therapeutic targets by further elucidating 
      the signaling molecules involved in epileptogenesis.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - McDaniel, Sharon S
AU  - McDaniel SS
AD  - Department of Neurology and the Hope Center for Neurological Disorders, 
      Washington University School of Medicine, St. Louis, MO 63110, USA.
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
GR  - R01 NS056872-06/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110224
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Anticonvulsants)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Anticonvulsants/*administration & dosage
MH  - Brain/drug effects/*metabolism
MH  - Encephalitis/complications/*metabolism/*prevention & control
MH  - Epilepsy/complications/*metabolism/*prevention & control
MH  - Humans
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC3109223
MID - NIHMS282581
EDAT- 2011/03/01 06:00
MHDA- 2012/03/03 06:00
PMCR- 2012/06/27
CRDT- 2011/03/01 06:00
PHST- 2010/06/03 00:00 [received]
PHST- 2011/01/25 00:00 [revised]
PHST- 2011/02/15 00:00 [accepted]
PHST- 2011/03/01 06:00 [entrez]
PHST- 2011/03/01 06:00 [pubmed]
PHST- 2012/03/03 06:00 [medline]
PHST- 2012/06/27 00:00 [pmc-release]
AID - S0304-3940(11)00204-7 [pii]
AID - 10.1016/j.neulet.2011.02.037 [doi]
PST - ppublish
SO  - Neurosci Lett. 2011 Jun 27;497(3):231-9. doi: 10.1016/j.neulet.2011.02.037. Epub 
      2011 Feb 24.