ArticleCell2014
Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions.
Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 203 papers, 1 of them a synthesis 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.
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Who cites it
203 citing papers in PubMed, 1 synthesis or guideline pooled it, 345 citations in OpenAlex.
- A meta-analysis of the effect of binge drinking on the oral microbiome and its relation to Alzheimer's disease.Scientific reports · 2020Pooled it
- Mitochondrial-Epigenetic Crosstalk in Autism Spectrum Disorder: Linking Cellular Stress to Synaptic Dysfunction and Treatment Resistance.Molecular neurobiology · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Viral Microglia Reprogramming Clears Oligomeric Neurotoxic Debris.bioRxiv : the preprint server for biology · 2026Article
- Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons.Life science alliance · 2026Article
- Transcriptional regulation of human NMNAT2: insights from 3D genome sequencing and bioinformatics.The FEBS journal · 2026Article
- SNCA triplication disrupts proteostasis and extracellular architecture prior to neurodegeneration in human midbrain organoids.NPJ Parkinson's disease · 2026Article
- Transcriptional readthrough at Atf4 locus suppresses Rps19bp1 and impairs heart development.Cardiovascular research · 2026Article
- Low concentrations of amyloid-beta oligomers induce synaptogenesis characteristic for mild cognitive impairment and alter the de novo proteome.Translational psychiatry · 2026Article
- Impaired BDNF-TrkB trafficking and signalling in Down syndrome basal forebrain neurons.Cell death & disease · 2026Article
- Therapeutic Options for Alzheimer's Disease and Aging-Associated Cognitive Decline: State of the Art in the ACH2.0 Paradigm.International journal of molecular sciences · 2026Review
- A central role for PINK1 in governing local mitochondrial biogenesis and degradation in neurons.Cellular and molecular life sciences : CMLS · 2026Review
- Alzheimer's disease risk geneBrain communications · 2026Article
- The mRNA Expression Levels of General Transcription Factors Altered in Alzheimer Cases Possibly Due to Amyloid Beta 1-42 Exposure.Noro psikiyatri arsivi · 2026Article
- Fasted-State Aerobic Exercise Enhances Cognition and Hippocampal BDNF Signaling in an Alzheimer's Disease Rat Model.Neurochemical research · 2025Article
- Vesicular Rps6 Released by Astrocytes in an Experimental Model of AD Regulates Local Translation and Enhances Synaptic Integrity in Neurones.Journal of extracellular vesicles · 2025Article
- RNA-binding protein IMP1/ZBP1 directs local translation in microglial processes to regulate motility and phagocytosis during inflammation.PLoS biology · 2025Article
- Epigenetic Mechanisms Shaping Spine Regulation: Unveiling the Role of Cytoskeletal Dynamics and Localized Protein Synthesis.Molecular neurobiology · 2025Review
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- Exploring the effects of squalene in the PERK/ATF4/eIF2α/CHOP signalling pathway in an in vitro Alzheimer Disease model and in silico approach.Metabolic brain disease · 2025Article
143 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
In Alzheimer's disease (AD) brain, exposure of axons to Aβ causes pathogenic changes that spread retrogradely by unknown mechanisms, affecting the entire neuron. We found that locally applied Aβ1-42 initiates axonal synthesis of a defined set of proteins including the transcription factor ATF4. Inhibition of local translation and retrograde transport or knockdown of axonal Atf4 mRNA abolished Aβ-induced ATF4 transcriptional activity and cell loss. Aβ1-42 injection into the dentate gyrus (DG) of mice caused loss of forebrain neurons whose axons project to the DG. Protein synthesis and Atf4 mRNA were upregulated in these axons, and coinjection of Atf4 siRNA into the DG reduced the effects of Aβ1-42 in the forebrain. ATF4 protein and transcripts were found with greater frequency in axons in the brain of AD patients. These results reveal an active role for intra-axonal translation in neurodegeneration and identify ATF4 as a mediator for the spread of AD pathology.
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What OpenQuestion 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 OpenQuestion graph.