Dysregulation of Mammalian Target of Rapamycin Signaling in Mouse Models of Autism
Open accessAbstract
The mammalian target of rapamycin (mTOR) is a central regulator of a diverse array of cellular processes, including cell growth, proliferation, autophagy, translation, and actin polymerization. Components of the mTOR cascade are present at synapses and influence synaptic plasticity and spine morphogenesis. A prevailing view is that the study of mTOR and its role in autism spectrum disorders (ASDs) will elucidate the molecular mechanisms by which mTOR regulates neuronal function under physiological and pathological conditions. Although many ASDs arise as a result of mutations in genes with multiple molecular functions, they appear to converge on common biological pathways that give rise to autism-relevant behaviors. Dysregulation of mTOR signaling has been identified as a phenotypic feature common to fragile X syndrome, tuberous sclerosis complex 1 and 2, neurofibromatosis 1, phosphatase and tensin homolog, and potentially Rett syndrome. Below are a summary of topics covered in a symposium that presents dysregulation of mTOR as a unifying theme in a subset of ASDs.
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MIA alters key components of the TSC/mTOR signaling pathway with ultimate activation of the translation initiation factor EIF4E, which is predicted to alter regulation of neural progenitor cell divisions during midgestation.
“Consistently, we found that MIA alters key components of the TSC/mTOR signaling pathway with ultimate activation of the translation initiation factor EIF4E which is predicted to alter the regulation of neural progenitor cell divisions during midgestation [127, 156–158].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [157]
mTOR kinase plays pivotal roles as a master regulator to integrate environmental cues and to modulate translation, cell growth, survival and proliferation.
“Of note, mTOR kinase plays pivotal roles as a master regulator to integrate environmental cues and to modulate translation, cell growth, survival and proliferation.84”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [84]
Dysregulation of mTOR-dependent signaling pathways has been found in ASD, Fragile X Syndrome, and Rett Syndrome.
“Dysregulation of mTOR-dependent signaling pathways has been found in ASD, Fragile X Syndrome, and Rett Syndrome.84”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [84]
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- Authors
- Huber, K. M., Klann, E., Costa-Mattioli, M., & Zukin, R. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- New York University (US)
- Albert Einstein College of Medicine (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-10-14
- Volume
- 35
- Issue
- 41
- Pages
- 13836-13842
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4604222
- OpenAlex
- W2176535580
- Cited by
- 167
- References
- 51
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 15 · 2022: 22 · 2021: 18 · 2020: 16 · 2019: 19 · 2018: 25 · 2017: 22 · 2016: 10
- FWCI
- 12.98
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH096816)
- National Institute of Neurological Disorders and Stroke (R01NS045711, R01NS047384, R01NS076708)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- mTOR signaling, autism spectrum disorder, fragile X syndrome, tuberous sclerosis complex, neurofibromatosis type 1, PTEN, Rett syndrome, synaptic plasticity, autophagy, mouse models of autism
- MeSH terms
- Animals, Autistic Disorder, Disease Models, Animal, Humans, Models, Biological, Signal Transduction, Sirolimus
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