PMID- 27049136
OWN - NLM
STAT- MEDLINE
DCOM- 20170320
LR  - 20220330
IS  - 1096-1186 (Electronic)
IS  - 1043-6618 (Linking)
VI  - 107
DP  - 2016 May
TI  - mTOR pathway inhibition as a new therapeutic strategy in epilepsy and 
      epileptogenesis.
PG  - 333-343
LID - S1043-6618(16)30255-9 [pii]
LID - 10.1016/j.phrs.2016.03.039 [doi]
AB  - Several preclinical and some clinical studies have revealed that the mammalian 
      target of rapamycin (mTOR) signaling pathway is involved in both genetic and 
      acquired epilepsy syndromes. Excessive activation of mTOR signaling, as a 
      consequence of loss-of-function of genes encoding for tuberous sclerosis complex 
      (TSC) 1 and 2, is linked to the development of cortical malformations and 
      epilepsy. This mTOR hyperactivation is associated with different epileptogenic 
      conditions under the term of 'mTORopathies' such as tuberous sclerosis, focal 
      cortical dysplasia, hemimegalencephaly and ganglioglioma. mTOR overactivation 
      produces brain abnormalities that include dysplastic neurons, abnormal cortical 
      organization and astrogliosis. mTOR inhibitors (e.g. rapamycin) have consistent 
      protective effects in various genetic (e.g. TSC models and WAG/Rij rats) and 
      acquired (e.g. kainate or pilocarpine post-status epilepticus) epilepsy animal 
      models. Furthermore, clinical studies in patients with TSC and cortical dysplasia 
      (CD) have confirmed the effectiveness of mTOR inhibitors also in epileptic 
      patients. Therefore, mTOR is currently a very good candidate as a target for 
      epilepsy and epileptogenesis. This review describes the relevance of the mTOR 
      pathway to epileptogenesis and its potential as a therapeutic target in epilepsy 
      treatment by presenting the most recent findings on mTOR inhibitors.
CI  - Copyright (c) 2016 Elsevier Ltd. All rights reserved.
FAU - Citraro, Rita
AU  - Citraro R
AD  - Department of Science of Health, School of Medicine and Surgery, University of 
      Catanzaro, Italy.
FAU - Leo, Antonio
AU  - Leo A
AD  - Department of Science of Health, School of Medicine and Surgery, University of 
      Catanzaro, Italy.
FAU - Constanti, Andrew
AU  - Constanti A
AD  - Department of Pharmacology, UCL School of Pharmacy, 29/39 Brunswick Square, 
      London, United Kingdom, UK.
FAU - Russo, Emilio
AU  - Russo E
AD  - Department of Science of Health, School of Medicine and Surgery, University of 
      Catanzaro, Italy.
FAU - De Sarro, Giovambattista
AU  - De Sarro G
AD  - Department of Science of Health, School of Medicine and Surgery, University of 
      Catanzaro, Italy. Electronic address: desarro@unicz.it.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20160402
PL  - Netherlands
TA  - Pharmacol Res
JT  - Pharmacological research
JID - 8907422
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Epilepsy/*drug therapy/metabolism
MH  - Humans
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Animal epilepsy models
OT  - Epilepsy
OT  - Epileptogenesis
OT  - Tuberous sclerosis complex
OT  - mTOR
OT  - mTOR inhibitors
EDAT- 2016/04/07 06:00
MHDA- 2017/03/21 06:00
CRDT- 2016/04/07 06:00
PHST- 2016/01/15 00:00 [received]
PHST- 2016/03/23 00:00 [revised]
PHST- 2016/03/31 00:00 [accepted]
PHST- 2016/04/07 06:00 [entrez]
PHST- 2016/04/07 06:00 [pubmed]
PHST- 2017/03/21 06:00 [medline]
AID - S1043-6618(16)30255-9 [pii]
AID - 10.1016/j.phrs.2016.03.039 [doi]
PST - ppublish
SO  - Pharmacol Res. 2016 May;107:333-343. doi: 10.1016/j.phrs.2016.03.039. Epub 2016 
      Apr 2.