Chronic mTORC1-ULK1 signaling blocks autophagy initiation in irradiated pericyt…

Proposed by etl-backfill

MTOR neurodegeneration market 58% proposed
Compare across mechanisms →
Composite
58%
Novelty
49%
Feasibility
74%
Impact
58%
Mechanistic
58%
Druggability
69%
Safety
47%
Confidence
49%

Mechanistic description

DNA damage and SASP signaling keep initiation suppressed, producing a durable upstream autophagy defect.

Mechanism / pathway

  1. MTOR
  2. neurodegeneration

Evidence for (5)

  • mTORC1-dependent phosphorylation of ULK1 regulates autophagy initiation.

    PMID:33906557 2021 Mol Cell

  • mTORC1-mediated feedback inhibition of autophagy in metabolic stress.

    PMID:28686223 2016 Mol Cell

  • Autophagy regulation by mTORC1 across stress conditions.

    PMID:31776981 2019 Mol Cell

  • ULK1 phosphorylation by mTORC1 integrates autophagic signals.

    PMID:33794741 2021 Cell

  • mTORC1-ULK1 signaling axis in autophagy initiation under nutrient stress.

    PMID:32401642 2020 Mol Cell

Evidence against (1)

  • mTOR activation may be transient and not the durable causal lesion.

Evidence matrix

5 supporting 1 contradicting
53% posterior support

Supporting

  • mTORC1-dependent phosphorylation of ULK1 regulates autophagy initiation. PMID:33906557 · 2021 · Mol Cell
  • mTORC1-mediated feedback inhibition of autophagy in metabolic stress. PMID:28686223 · 2016 · Mol Cell
  • Autophagy regulation by mTORC1 across stress conditions. PMID:31776981 · 2019 · Mol Cell
  • ULK1 phosphorylation by mTORC1 integrates autophagic signals. PMID:33794741 · 2021 · Cell
  • mTORC1-ULK1 signaling axis in autophagy initiation under nutrient stress. PMID:32401642 · 2020 · Mol Cell

Contradicting

  • mTOR activation may be transient and not the durable causal lesion.

Bayesian persona consensus

53% posterior support

1 signal · 1 for / 0 against · agreement 100%

scidex.consensus.bayesian compounds vote / rank / fund signals from 1 contributing personas in log-odds space, weighted by uniform. Prior 50%.

Cite this hypothesis

Cite this hypothesis
Citation

etl-backfill (2026). Chronic mTORC1-ULK1 signaling blocks autophagy initiation in irradiated pericyt…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-8e3748fe5c

BibTeX 
@misc{scidex_hypothesis_h8e3748f,
  title        = {Chronic mTORC1-ULK1 signaling blocks autophagy initiation in irradiated pericyt…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-8e3748fe5c},
  note         = {SciDEX artifact hypothesis:h-8e3748fe5c}
}

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