Cited by 441PI3K/AKT/mTOR signaling in cancerGenetics and Neurodevelopmental DisordersTuberous Sclerosis Complex Research

The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.

Pharmacological Inhibition of mTORC1 Suppresses Anatomical, Cellular, and Behavioral Abnormalities in Neural-Specific Pten Knock-Out Mice

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Abstract

PTEN (phosphatase and tensin homolog deleted on chromosome ten) is a lipid phosphatase that counteracts the function of phosphatidylinositol-3 kinase (PI3K). Loss of function of PTEN results in constitutive activation of AKT and downstream effectors and correlates with many human cancers, as well as various brain disorders, including macrocephaly, seizures, Lhermitte–Duclos disease, and autism. We previously generated a conditional Pten knock-out mouse line with Pten loss in limited postmitotic neurons in the cortex and hippocampus.Pten-null neurons developed neuronal hypertrophy and loss of neuronal polarity. The mutant mice exhibited macrocephaly and behavioral abnormalities reminiscent of certain features of human autism. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can prevent and reverse neuronal hypertrophy, resulting in the amelioration of a subset of PTEN-associated abnormal behaviors, providing evidence that the mTORC1 pathway downstream of PTEN is critical for this complex phenotype.

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Crossref · 10.1523/jneurosci.5685-08.2009

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Metadata

Authors
Zhou, J., Blundell, J., Ogawa, S., Kwon, C.-H., Zhang, W., Sinton, C., Powell, C. M., & Parada, L. F.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • The University of Texas at Dallas (US)
Venue
The Journal of Neuroscience
Published
2009-02-11
Volume
29
Issue
6
Pages
1773-1783
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2017097994
Cited by
441
References
52
Citations by year
2026: 10 · 2025: 20 · 2024: 17 · 2023: 17 · 2022: 19 · 2021: 22 · 2020: 49 · 2019: 16 · 2018: 24 · 2017: 28 · 2016: 22 · 2015: 37 · 2014: 31 · 2013: 32 · 2012: 39
FWCI
12.74
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
Funders
  • Autism Speaks (AS1270, AS2126)
  • Simons Foundation
  • National Institute of Mental Health (K08MH065975, R01MH081164)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD065290)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
  • Health Sciences › Medicine › Genetics (clinical) › Tuberous Sclerosis Complex Research
Keywords
PTEN, mTORC1, rapamycin, neuronal hypertrophy, neuronal polarity, macrocephaly, autism-like behavior, postmitotic neurons, PI3K/Akt signaling, Lhermitte-Duclos disease, seizures, hippocampus, cortex
MeSH terms
Animals, Autistic Disorder, Female, Male, Mice, Inbred C57BL, Neurons, Transcription Factors, Mice, Knockout, Sirolimus, PTEN Phosphohydrolase, Mice

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