ReviewJournal of neuropathology and experimental neurology2020
The Integrated Stress Response and Phosphorylated Eukaryotic Initiation Factor 2α in Neurodegeneration.
Review in Journal of neuropathology and experimental neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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
81 citing papers in PubMed, 134 citations in OpenAlex.
- Distinct cell type-specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Targeting the integrated stress response or Ataxin-2 alleviates neurodegeneration in PolyGR models of C9orf72 associated frontotemporal dementia and amyotrophic lateral sclerosis.Acta neuropathologica communications · 2026Article
- Disruption of CSF-1 receptor-mediated metal ion homeostasis in the murine brain promotes neurodegenerative disease.The Journal of clinical investigation · 2026Article
- Spatial Single-Cell Proteomics Reveals Molecular Trajectories Of Tangle-Bearing Neurons In Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Axonal distribution of mitochondria maintains neuronal autophagy during aging via eIF2β.eLife · 2026Article
- Cockayne syndrome mutation in XPG activate the integrated stress response.Human genetics · 2026Article
- Inhibition of the integrated stress response rescues a histidyl-tRNA synthetase variant associated with Charcot-Marie-Tooth disease.NAR molecular medicine · 2026Article
- Integrated Stress Response and Necroptosis Drive Epithelial Dysfunction in Crohn's Disease: Repurposing Cancer Drugs for Permeability Barrier Healing.Gastro hep advances · 2026Article
- Dysregulated neuronal mRNA transport and translation in FTD/ALS.NPJ dementia · 2026Review
- Roles of the integrated stress response in regulation of inflammatory reactions.Frontiers in immunology · 2026Review
- Proteasome and Ribosome Ubiquitination in Retinal Pigment Epithelial (RPE) Cells in Response to Oxidized Low-Density Lipoprotein (OxLDL).Biomedicines · 2025Article
- Proteostasis network response to environmental chronic stress: linking survival to protein aggregation in a human neuroblastoma cellular model.Cellular and molecular life sciences : CMLS · 2025Article
- A Phase I Clinical Study and In Vivo Findings with PT-112, a Novel Immunogenic Cell Death-Inducing Small Molecule, in Relapsed or Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- Dual Nature of Mitochondrial Integrated Stress Response: Molecular Switches from Protection to Pathology.Genes · 2025Review
- Saturated phosphatidic acids induce mTORC1-driven integrated stress response contributing to glucolipotoxicity in hepatocytes.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Inflammatory cytokine upd3 induces axon length-dependent synapse removal by glia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Unravelling the role of protein kinase R (PKR) in neurodegenerative disease: a review.Molecular biology reports · 2025Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The proposed molecular mechanisms underlying neurodegenerative pathogenesis are varied, precluding the development of effective therapies for these increasingly prevalent disorders. One of the most consistent observations across neurodegenerative diseases is the phosphorylation of eukaryotic initiation factor 2α (eIF2α). eIF2α is a translation initiation factor, involved in cap-dependent protein translation, which when phosphorylated causes global translation attenuation. eIF2α phosphorylation is mediated by 4 kinases, which, together with their downstream signaling cascades, constitute the integrated stress response (ISR). While the ISR is activated by stresses commonly observed in neurodegeneration, such as oxidative stress, endoplasmic reticulum stress, and inflammation, it is a canonically adaptive signaling cascade. However, chronic activation of the ISR can contribute to neurodegenerative phenotypes such as neuronal death, memory impairments, and protein aggregation via apoptotic induction and other maladaptive outcomes downstream of phospho-eIF2α-mediated translation inhibition, including neuroinflammation and altered amyloidogenic processing, plausibly in a feed-forward manner. This review examines evidence that dysregulated eIF2a phosphorylation acts as a driver of neurodegeneration, including a survey of observations of ISR signaling in human disease, inspection of the overlap between ISR signaling and neurodegenerative phenomenon, and assessment of recent encouraging findings ameliorating neurodegeneration using developing pharmacological agents which target the ISR. In doing so, gaps in the field, including crosstalk of the ISR kinases and consideration of ISR signaling in nonneuronal central nervous system cell types, are highlighted.
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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.