REST-like neuronal silencing programs suppress MAPT in severe proteostatic stre…

Mechanistic description

A broader neuronal downscaling program contributes to tau repression when stress becomes chronic or severe.

Mechanism / pathway

REST
→
neurodegeneration

Evidence for (5)

REST and REST-dependent programs in neuronal gene regulation and disease.

PMID:12130773 2002 J Neurosci Res
REST deficiency drives tau pathology through dysregulation of synaptic and neuronal genes.

PMID:37919281 2023 Neurobiol Dis
REST regulates tau and neurodegenerative gene programs in aging brain.

PMID:41039568 2024 Neurobiol Dis
REST is a critical regulator of neuronal genome and proteostasis in aging.

PMID:31793911 2018 Nat Neurosci
Loss of REST function in neurodegeneration leads to synaptic gene dysregulation.

PMID:35346299 2022 Neurobiol Dis

Evidence against (1)

This program may emerge too late to explain the primary suppressive event.

Evidence matrix

5 supporting 1 contradicting

83% supporting

Supporting

REST and REST-dependent programs in neuronal gene regulation and disease. PMID:12130773 · 2002 · J Neurosci Res
REST deficiency drives tau pathology through dysregulation of synaptic and neuronal genes. PMID:37919281 · 2023 · Neurobiol Dis
REST regulates tau and neurodegenerative gene programs in aging brain. PMID:41039568 · 2024 · Neurobiol Dis
REST is a critical regulator of neuronal genome and proteostasis in aging. PMID:31793911 · 2018 · Nat Neurosci
Loss of REST function in neurodegeneration leads to synaptic gene dysregulation. PMID:35346299 · 2022 · Neurobiol Dis

Contradicting

This program may emerge too late to explain the primary suppressive event.

Cite this hypothesis

Citation

etl-backfill (2026). REST-like neuronal silencing programs suppress MAPT in severe proteostatic stre…. SciDEX hypothesis. https://prism.scidex.ai/hypotheses/h-6ca2dbc5f0

BibTeX

@misc{scidex_hypothesis_h6ca2dbc,
  title        = {REST-like neuronal silencing programs suppress MAPT in severe proteostatic stre…},
  author       = {etl-backfill},
  year         = {2026},
  howpublished = {SciDEX hypothesis},
  url          = {https://prism.scidex.ai/hypotheses/h-6ca2dbc5f0},
  note         = {SciDEX artifact hypothesis:h-6ca2dbc5f0}
}