ArticleThe Journal of clinical investigation2018
Tuberous sclerosis complex-associated CNS abnormalities depend on hyperactivation of mTORC1 and Akt.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Single nuclei transcriptomics reveals cellular diversity in TSC subependymal giant cell astrocytomas.iScience · 2025Article
- A bitopic mTORC inhibitor reverses phenotypes in a tuberous sclerosis complex model.Scientific reports · 2025Article
- TSC-mTORC1 Pathway in Postnatal V-SVZ Neurodevelopment.Biomolecules · 2025Review
- Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate.Stem cell research & therapy · 2025Review
- A case report and review of rheumatoid arthritis co-occurring with tuberous sclerosis complex, a rare occurrence.Frontiers in immunology · 2024Review
- Article
- Targeting mTOR Pathway in PTEN Deleted Newly Isolated Chordoma Cell Line.Journal of personalized medicine · 2023Article
- Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Hyperactivation of mTORC1 in a double hit mutant zebrafish model of tuberous sclerosis complex causes increased seizure susceptibility and neurodevelopmental abnormalities.Frontiers in cell and developmental biology · 2022Article
- Isolation and Culture of Neural Stem/Progenitor Cells from the Postnatal Periventricular Region.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.Immunity · 2021Article
- The Characterization of a Subependymal Giant Astrocytoma-Like Cell Line from Murine Astrocyte with mTORC1 Hyperactivation.International journal of molecular sciences · 2021Article
- Rapamycin increases the incidence of neuropsychiatric illness in kidney transplant patients through the suppression of neural stem cells.Translational psychiatry · 2020Article
- The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC).Frontiers in neuroanatomy · 2020Review
- Autophagic lipid metabolism sustains mTORC1 activity in TSC-deficient neural stem cells.Nature metabolism · 2019Article
- Yokukansan, a Kampo medicine, enhances the level of neuronal lineage markers in differentiated P19 embryonic carcinoma cells.Heliyon · 2019Article
- Dynamics and genomic landscape of CD8Nature · 2019Article
- Sestrin modulator NV-5138 produces rapid antidepressant effects via direct mTORC1 activation.The Journal of clinical investigation · 2019Article
- Location-dependent maintenance of intrinsic susceptibility to mTORC1-driven tumorigenesis.Life science alliance · 2019Article
- Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors.Medical sciences (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tuberous sclerosis complex (TSC) is a dominantly inherited disease caused by hyperactivation of the mTORC1 pathway and characterized by the development of hamartomas and benign tumors, including in the brain. Among the neurological manifestations associated with TSC, the tumor progression of static subependymal nodules (SENs) into subependymal giant cell astrocytomas (SEGAs) is one of the major causes of morbidity and shortened life expectancy. To date, mouse modeling has failed in reproducing these 2 lesions. Here we report that simultaneous hyperactivation of mTORC1 and Akt pathways by codeletion of Tsc1 and Pten, selectively in postnatal neural stem cells (pNSCs), is required for the formation of bona fide SENs and SEGAs. Notably, both lesions closely recapitulate the pathognomonic morphological and molecular features of the corresponding human abnormalities. The establishment of long-term expanding pNSC lines from mouse SENs and SEGAs made possible the identification of mTORC2 as one of the mediators conferring tumorigenic potential to SEGA pNSCs. Notably, in spite of concurrent Akt hyperactivation in mouse brain lesions, single mTOR inhibition by rapamycin was sufficient to strongly impair mouse SEGA growth. This study provides evidence that, concomitant with mTORC1 hyperactivation, sustained activation of Akt and mTORC2 in pNSCs is a mandatory step for the induction of SENs and SEGAs, and, at the same time, makes available an unprecedented NSC-based in vivo/in vitro model to be exploited for identifying actionable targets in TSC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.