PMID- 19761448
OWN - NLM
STAT- MEDLINE
DCOM- 20090929
LR  - 20211203
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Linking)
VI  - 50 Suppl 9
DP  - 2009 Oct
TI  - Focal brain malformations: seizures, signaling, sequencing.
PG  - 3-8
LID - 10.1111/j.1528-1167.2009.02289.x [doi]
AB  - Focal malformations of cortical development are highly associated with 
      intractable epilepsy in children and adults. Most patients with focal cortical 
      malformations and epilepsy will require epilepsy surgery. Recent studies have 
      provided new insights into the developmental pathogenesis of cortical 
      malformations specifically relating to alterations in cell signaling though the 
      mammalian target of rapamycin (mTOR) pathway. Focal cortical dysplasias, 
      hemimegalencephaly, and tubers in tuberous sclerosis complex all exhibit evidence 
      for hyperactive mTOR signaling, suggesting that these disorders form a spectrum 
      of malformations or "TORopathies" characterized by disorganized cortical 
      lamination, cytomegaly, and intractable seizures. Alterations in mTOR activity in 
      focal brain malformations provide a potential pathogenic pathway to investigate 
      for gene mutations and to exploit for animal models. Most importantly, however, 
      if select focal cortical malformations result from enhanced mTOR signaling, new 
      therapeutic antiepileptic compounds, such as rapamycin, can be designed and 
      tested that specifically target mTOR signaling.
FAU - Crino, Peter B
AU  - Crino PB
AD  - Department of Neurology, PENN Epilepsy Center, University of Pennsylvania, 
      Philadelphia, Pennsylvania 19104, USA. peter.crino@uphs.upenn.edu
LA  - eng
GR  - R01NS045877/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - 0 (Anticonvulsants)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Anticonvulsants/pharmacology/therapeutic use
MH  - Disease Models, Animal
MH  - Drug Design
MH  - Epilepsies, Partial/genetics/pathology/surgery
MH  - Gene Expression
MH  - Humans
MH  - Malformations of Cortical Development/*genetics/*pathology/surgery
MH  - Mice
MH  - Mutation/genetics
MH  - Protein Kinases/*genetics
MH  - Signal Transduction/genetics
MH  - Sirolimus/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis/genetics/pathology/surgery
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/drug effects/genetics
EDAT- 2009/09/26 06:00
MHDA- 2009/09/30 06:00
CRDT- 2009/09/19 06:00
PHST- 2009/09/19 06:00 [entrez]
PHST- 2009/09/26 06:00 [pubmed]
PHST- 2009/09/30 06:00 [medline]
AID - EPI2289 [pii]
AID - 10.1111/j.1528-1167.2009.02289.x [doi]
PST - ppublish
SO  - Epilepsia. 2009 Oct;50 Suppl 9:3-8. doi: 10.1111/j.1528-1167.2009.02289.x.