PMID- 29338461
OWN - NLM
STAT- MEDLINE
DCOM- 20190307
LR  - 20211204
IS  - 1744-8360 (Electronic)
IS  - 1473-7175 (Linking)
VI  - 18
IP  - 3
DP  - 2018 Mar
TI  - mTOR dysregulation and tuberous sclerosis-related epilepsy.
PG  - 185-201
LID - 10.1080/14737175.2018.1428562 [doi]
AB  - The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for 
      proper neural network development, and it is involved in epileptogenesis 
      triggered by both genetic or acquired factors. Areas covered. The robust mTOR 
      signaling deregulation observed in a large spectrum of epileptogenic 
      developmental pathologies, such as focal cortical dysplasias and tuberous 
      sclerosis complex (TSC), has been linked to germline and somatic mutations in 
      mTOR pathway regulatory genes, increasing the spectrum of 'mTORopathies'. The 
      significant advances in the field of TSC allowed for the validation of emerging 
      hypotheses on the mechanisms of epileptogenesis and the identification of 
      potential new targets of therapy. Recently, a double-blind phase III randomized 
      clinical trial on patients with TSC related epilepsy, demonstrated that 
      adjunctive treatment with mTOR inhibition is effective and safe in reducing focal 
      drug resistant seizures. Expert commentary. mTOR signaling dysregulation 
      represents a common pathogenic mechanism in a subset of malformations of cortical 
      development, sharing histopathological and clinical features, including epilepsy, 
      autism, and intellectual disability. EXIST-3 trial provided the first evaluation 
      of the optimal dosage, conferring a higher chance of reducing seizure frequency 
      and severity, with adverse events being similar to what observed with lower 
      dosages.
FAU - Curatolo, Paolo
AU  - Curatolo P
AD  - a Child Neurology and Psychiatry Unit, Systems Medicine Department , Tor Vergata 
      University Hospital , Rome , Italy.
FAU - Moavero, Romina
AU  - Moavero R
AUID- ORCID: 0000-0002-6200-060X
AD  - a Child Neurology and Psychiatry Unit, Systems Medicine Department , Tor Vergata 
      University Hospital , Rome , Italy.
AD  - b Child Neurology Unit, Neuroscience and Neurorehabilitation Department , 
      "Bambino Gesu" Children's Hospital, IRCCS , Rome , Italy.
FAU - van Scheppingen, Jackelien
AU  - van Scheppingen J
AD  - c Department of (Neuro)Pathology, Academic Medical Center , University of 
      Amsterdam , Amsterdam , The Netherlands.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - c Department of (Neuro)Pathology, Academic Medical Center , University of 
      Amsterdam , Amsterdam , The Netherlands.
AD  - d Stichting Epilepsie Instellingen Nederland (SEIN) , The Netherlands.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180127
PL  - England
TA  - Expert Rev Neurother
JT  - Expert review of neurotherapeutics
JID - 101129944
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/therapeutic use
MH  - Epilepsy/*complications/drug therapy/genetics/*physiopathology
MH  - Humans
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*physiology
MH  - Tuberous Sclerosis/*complications/physiopathology
OTO - NOTNLM
OT  - Epilepsy
OT  - epileptogenesis
OT  - everolimus
OT  - mTOR inhibitors
OT  - mTORopathies
OT  - malformations
OT  - rapamycin
OT  - tuberous sclerosis complex
EDAT- 2018/01/18 06:00
MHDA- 2019/03/08 06:00
CRDT- 2018/01/18 06:00
PHST- 2018/01/18 06:00 [pubmed]
PHST- 2019/03/08 06:00 [medline]
PHST- 2018/01/18 06:00 [entrez]
AID - 10.1080/14737175.2018.1428562 [doi]
PST - ppublish
SO  - Expert Rev Neurother. 2018 Mar;18(3):185-201. doi: 10.1080/14737175.2018.1428562. 
      Epub 2018 Jan 27.