Brain Symptoms of Tuberous Sclerosis Complex: Pathogenesis and Treatment.
Animals
Brain
/ metabolism
Disease Management
Disease Models, Animal
Disease Susceptibility
Epilepsy
/ diagnosis
Genetic Predisposition to Disease
Humans
Symptom Assessment
TOR Serine-Threonine Kinases
/ metabolism
Tuberous Sclerosis
/ diagnosis
Tuberous Sclerosis Complex 1 Protein
/ genetics
Tuberous Sclerosis Complex 2 Protein
/ genetics
TSC
autism
epilepsy
epileptic encephalopathy
intellectual disability
mTOR inhibitor
mTORopathy
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
22 Jun 2021
22 Jun 2021
Historique:
received:
21
05
2021
revised:
16
06
2021
accepted:
19
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
24
7
2021
Statut:
epublish
Résumé
The mammalian target of the rapamycin (mTOR) system plays multiple, important roles in the brain, regulating both morphology, such as cellular size, shape, and position, and function, such as learning, memory, and social interaction. Tuberous sclerosis complex (TSC) is a congenital disorder caused by a defective suppressor of the mTOR system, the TSC1/TSC2 complex. Almost all brain symptoms of TSC are manifestations of an excessive activity of the mTOR system. Many children with TSC are afflicted by intractable epilepsy, intellectual disability, and/or autism. In the brains of infants with TSC, a vicious cycle of epileptic encephalopathy is formed by mTOR hyperactivity, abnormal synaptic structure/function, and excessive epileptic discharges, further worsening epilepsy and intellectual/behavioral disorders. Molecular target therapy with mTOR inhibitors has recently been proved to be efficacious for epilepsy in human TSC patients, and for autism in TSC model mice, indicating the possibility for pharmacological treatment of developmental synaptic disorders.
Identifiants
pubmed: 34206526
pii: ijms22136677
doi: 10.3390/ijms22136677
pmc: PMC8268912
pii:
doi:
Substances chimiques
TSC1 protein, human
0
TSC2 protein, human
0
Tuberous Sclerosis Complex 1 Protein
0
Tuberous Sclerosis Complex 2 Protein
0
MTOR protein, human
EC 2.7.1.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute of Public Health, Japan
ID : 20FC1043
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