Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function

Meikle L, Pollizzi K, Egnor A, Kramvis I, Lane H, Sahin M, Kwiatkowski DJ · 2008 · The Journal of neuroscience · Atlas ID MEI2008

What this study shows

mTOR inhibition rescues a neuronal tuberous-sclerosis model, supporting rapamycin for TSC neurology.

Abstract

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Tuberous sclerosis (TSC) is a hamartoma syndrome attributable to mutations in either TSC1 or TSC2 in which brain involvement causes epilepsy, mental retardation, and autism. We have reported recently a mouse neuronal model of TSC in which Tsc1 is ablated in most neurons during cortical development. We have tested rapamycin and RAD001, both mammalian target of rapamycin mTORC1 inhibitors, as potential therapeutic agents in this model. Median survival is improved from 33 d to more than 100 d; behavior, phenotype, and weight gain are all also markedly improved.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (Tsc1 neuronal KO)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (Tsc1 neuronal KO)
Journal	The Journal of neuroscience
Year	2008
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1523/JNEUROSCI.0955-08.2008 · PMID 18495876 · Free full text (PMC2633923)

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Rapamycin / RAD001 (mTORC1 inhibition)
Target	mTORC1 / Akt
Model	Mouse (Tsc1 neuronal KO)
Effect	mTOR inhibitors improve survival and function in a neuronal model of tuberous sclerosis

In the Atlas

Links in the pathway map

Supports Everolimus inhibits mTORC1
Supports Rapamycin inhibits mTORC1

Open questions that cite this study

Cited as supporting evidence for the open question Brain-penetrant mTOR inhibition clears aggregates in models, but human dosing has not been shown to reach the brain — and mTORC2 is needed for memory in mice.

Cite this paper

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Meikle, L., Pollizzi, K., Egnor, A., Kramvis, I., Lane, H., Sahin, M., & Kwiatkowski, D. J. (2008). Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function. The Journal of neuroscience. https://doi.org/10.1523/JNEUROSCI.0955-08.2008

@article{MEI2008,
  author       = {Meikle, L. and Pollizzi, K. and Egnor, A. and Kramvis, I. and Lane, H. and Sahin, M. and Kwiatkowski, D. J.},
  title        = {{Response of a neuronal model of tuberous sclerosis to mammalian target of rapamycin (mTOR) inhibitors: effects on mTORC1 and Akt signaling lead to improved survival and function}},
  journal      = {The Journal of neuroscience},
  year         = {2008},
  doi          = {10.1523/JNEUROSCI.0955-08.2008},
  note         = {PMID: 18495876},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record MEI2008) [Data set]. https://mtor-atlas.org/study/MEI2008/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_MEI2008,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record MEI2008},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/MEI2008/},
  doi          = {10.5281/zenodo.22059963}
}

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