Research paper
Disruption of mTORC1 rescues neuronal overgrowth and synapse function disturbed by loss of PTEN
Mechanistic study demonstrating that mTORC1 disruption rescues neuronal overgrowth and synaptic dysfunction in the context of PTEN loss. Identifies mTORC1 as sufficient to mediate the PTEN-loss phenotype and a viable therapeutic target.
Tariq K, et al.
Markdown path
content/research/papers/2022-tariq-pten-mtorc1-neuronal-rescue.mdFindings
Mechanistic study demonstrating that mTORC1 disruption rescues neuronal overgrowth and synaptic dysfunction in the context of PTEN loss. Identifies mTORC1 as sufficient to mediate the PTEN-loss phenotype and a viable therapeutic target.
Why it may matter for Levi
Strengthens the rapalog rationale if a PTEN or PI3K-AKT-mTOR variant is identified in Levi. Complementary to Lasser 2024 - Tariq argues mTORC1-alone targeting is sufficient while Lasser argues dual mTORC1/mTORC2 may outperform. Both positions would inform precision-therapy selection and would need to be weighed against the specific variant identified. Empiric rapamycin without molecular confirmation remains unsupported.
Tariq et al. (2022) — Disruption of mTORC1 rescues neuronal overgrowth and synaptopathy in PTEN loss
Source
- Cell Reports, 2022.
- URL: https://www.sciencedirect.com/science/article/pii/S2211124722014358
Why this paper is in the corpus
Mechanistic study demonstrating that disrupting mTORC1 rescues neuronal overgrowth and synaptic dysfunction in the context of PTEN loss. Complements the Lasser 2024 paper already in the corpus (which established that PTEN loss hyperactivates both mTORC1 and mTORC2) by showing that mTORC1 is sufficient to mediate the phenotype and is a viable therapeutic target.
Key findings
- In PTEN-loss models, mTORC1 disruption rescued neuronal overgrowth and synaptic function.
- Identified mTORC1 as a mediator of the PTEN-loss neuronal phenotype.
- Provides mechanistic support for rapamycin / everolimus (mTORC1-selective inhibitors) as therapeutic strategies for PTEN-related disorders.
Levi-relevant takeaways
- Strengthens the rapalog rationale if a PTEN or PI3K-AKT-mTOR variant is identified in Levi.
- Complementary to Lasser 2024: Lasser argues dual mTORC1/mTORC2 inhibitors may outperform mTORC1-selective rapalogs; Tariq argues mTORC1-alone targeting is sufficient for neuronal rescue. Both positions inform precision-therapy selection and would need to be weighed against the specific variant identified.
- Reinforces that empiric rapamycin without molecular confirmation remains unsupported; molecular diagnosis should drive drug selection.
Citation note
Referenced as [25] in the 2026-04-21 user-supplied comprehensive DEE-SWAS / ESES / CSWS research report.