PMID- 33041976
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201013
IS  - 1664-2295 (Print)
IS  - 1664-2295 (Electronic)
IS  - 1664-2295 (Linking)
VI  - 11
DP  - 2020
TI  - Tuberous Sclerosis Complex as Disease Model for Investigating mTOR-Related 
      Gliopathy During Epileptogenesis.
PG  - 1028
LID - 10.3389/fneur.2020.01028 [doi]
LID - 1028
AB  - Tuberous sclerosis complex (TSC) represents the prototypic monogenic disorder of 
      the mammalian target of rapamycin (mTOR) pathway dysregulation. It provides the 
      rational mechanistic basis of a direct link between gene mutation and brain 
      pathology (structural and functional abnormalities) associated with a complex 
      clinical phenotype including epilepsy, autism, and intellectual disability. So 
      far, research conducted in TSC has been largely neuron-oriented. However, the 
      neuropathological hallmarks of TSC and other malformations of cortical 
      development also include major morphological and functional changes in glial 
      cells involving astrocytes, oligodendrocytes, NG2 glia, and microglia. These 
      cells and their interglial crosstalk may offer new insights into the common 
      neurobiological mechanisms underlying epilepsy and the complex cognitive and 
      behavioral comorbidities that are characteristic of the spectrum of 
      mTOR-associated neurodevelopmental disorders. This review will focus on the role 
      of glial dysfunction, the interaction between glia related to mTOR hyperactivity, 
      and its contribution to epileptogenesis in TSC. Moreover, we will discuss how 
      understanding glial abnormalities in TSC might give valuable insight into the 
      pathophysiological mechanisms that could help to develop novel therapeutic 
      approaches for TSC or other pathologies characterized by glial dysfunction and 
      acquired mTOR hyperactivation.
CI  - Copyright (c) 2020 Zimmer, Broekaart, Gruber, van Vliet, Muhlebner and Aronica.
FAU - Zimmer, Till S
AU  - Zimmer TS
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
FAU - Broekaart, Diede W M
AU  - Broekaart DWM
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
FAU - Gruber, Victoria-Elisabeth
AU  - Gruber VE
AD  - Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, 
      Vienna, Austria.
FAU - van Vliet, Erwin A
AU  - van Vliet EA
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
AD  - Swammerdam Institute for Life Sciences, Center for Neuroscience, University of 
      Amsterdam, Amsterdam, Netherlands.
FAU - Muhlebner, Angelika
AU  - Muhlebner A
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
FAU - Aronica, Eleonora
AU  - Aronica E
AD  - Department of (Neuro)Pathology, Amsterdam Neuroscience, Amsterdam University 
      Medical Centers, University of Amsterdam, Amsterdam, Netherlands.
AD  - Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200917
PL  - Switzerland
TA  - Front Neurol
JT  - Frontiers in neurology
JID - 101546899
PMC - PMC7527496
OTO - NOTNLM
OT  - astrocyte
OT  - epilepsy
OT  - epileptogenesis
OT  - glia
OT  - mammalian target of rapamycin (mTOR)
OT  - microglia
OT  - oligodendrocyte
OT  - tuberous sclerosis (TSC)
EDAT- 2020/10/13 06:00
MHDA- 2020/10/13 06:01
PMCR- 2020/09/17
CRDT- 2020/10/12 05:28
PHST- 2020/06/07 00:00 [received]
PHST- 2020/08/06 00:00 [accepted]
PHST- 2020/10/12 05:28 [entrez]
PHST- 2020/10/13 06:00 [pubmed]
PHST- 2020/10/13 06:01 [medline]
PHST- 2020/09/17 00:00 [pmc-release]
AID - 10.3389/fneur.2020.01028 [doi]
PST - epublish
SO  - Front Neurol. 2020 Sep 17;11:1028. doi: 10.3389/fneur.2020.01028. eCollection 
      2020.