ArticleNature2014
REST and stress resistance in ageing and Alzheimer's disease.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 466 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
466 citing papers in PubMed, 2 syntheses or guidelines pooled it, 774 citations in OpenAlex.
- Bibliometric and visual analysis of single-cell multiomics in neurodegenerative disease arrest studies.Frontiers in neurology · 2024Pooled it
- Tracing the origins of glioblastoma by investigating the role of gliogenic and related neurogenic genes/signaling pathways in GBM development: a systematic review.World journal of surgical oncology · 2022Pooled it
- Modulation of Amyloid-β and Tau in Alzheimer's Disease Plasma Neuronal-Derived Extracellular Vesicles by Cerebrolysin® and Donepezil.Journal of Alzheimer's disease : JAD · 2022Trial
- TripleBind: a generalizable deep learning framework for protein-nucleic acid and protein-ligand binding sites prediction based on pre-trained protein language models.Molecular diversity · 2026Article
- Review
- Protein-DNA Binding Sites Prediction via Integrating Pretrained Large Language Models and Contrastive Learning.Interdisciplinary sciences, computational life sciences · 2026Article
- Alzheimer's disease through the lens of mesenchymal drift: the collapse of cellular identity.BMB reports · 2026Review
- Systematic detection of predictive gene sets by semantics-based selection.BMC bioinformatics · 2026Article
- Molecular Networks and Key Regulators Underlying Resilience of the Human Brain to Aging and Dementia.Biomolecules · 2026Article
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Aging epigenome begins to change in age-related neurodegenerative diseases.Neural regeneration research · 2026Article
- Article
- Review
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer's disease-related hyperexcitability and brain network dysfunction.bioRxiv : the preprint server for biology · 2026Article
- MYC-driven gliosis impairs neuron-glia communication in amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Loss of REST associated with Alzheimer's disease pathology is ameliorated by NAD.Brain : a journal of neurology · 2026Article
- Transcription factors Lef1 and Rest stimulate recovery from depressive states.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Differential Gene Expression in Human Hippocampus With Aging.Aging cell · 2026Article
406 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.