ArticleNeuron2020
Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration.
Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers.
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Who cites it
141 citing papers in PubMed.
- Lcn2 Promotes Ferroptosis in Intracerebral Hemorrhage by Targeting Keap1 Tyr572 and Restricting Nrf2 Activation.MedComm · 2026Article
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
- Targeting MAPK-dependent pathways to modulate reactive astrocyte pathology in neurodegeneration.Communications biology · 2026Article
- Review
- The effect of astrocyte depletion and repopulation approaches in pathological condition of CNS.Acta neurologica Belgica · 2026Review
- Dynamic changes in excitability and viability of sporadic andFrontiers in cell and developmental biology · 2026Article
- Therapeutic strategies in prion disease: current evidence, translational challenges, and emerging directions.Frontiers in neuroscience · 2026Review
- Rigor & Reproducibility: pH Adjustments of Papain with L-Cysteine Dissociation Solutions and Cell Media Using Phenol Red Spectrophotometry.Biosensors · 2025Article
- Article
- Astrocytes as Metabolic Sensors Orchestrating Energy-Driven Brain Vulnerability in Alzheimer's Disease.Journal of neurochemistry · 2025Review
- Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.Brain : a journal of neurology · 2025Article
- Review
- Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons.Nature communications · 2025Article
- Article
- Preliminary exploration of endoplasmic reticulum stress transmission in astrocytes and neurons, and its mediators.Molecular medicine reports · 2025Article
- Downregulation of STAT3 transcription factor reverses synaptotoxic phenotype of reactive astrocytes associated with prion diseases.Acta neuropathologica communications · 2025Article
- Endoplasmic Reticulum Stress Drives Neuroinflammation Through Lipocalin 2 Upregulation in Retinal Microglia After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- TSG-6 Protects Against Cerebral Ischemia-Reperfusion Injury via Upregulating Hsp70-1B in Astrocytes.CNS neuroscience & therapeutics · 2025Article
- Mechanisms of astrocyte aging in reactivity and disease.Molecular neurodegeneration · 2025Review
- A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.Neuron · 2025Article
81 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors.
Funding
Abstract
Recent interest in astrocyte activation states has raised the fundamental question of how these cells, normally essential for synapse and neuronal maintenance, become pathogenic. Here, we show that activation of the unfolded protein response (UPR), specifically phosphorylated protein kinase R-like endoplasmic reticulum (ER) kinase (PERK-P) signaling-a pathway that is widely dysregulated in neurodegenerative diseases-generates a distinct reactivity state in astrocytes that alters the astrocytic secretome, leading to loss of synaptogenic function in vitro. Further, we establish that the same PERK-P-dependent astrocyte reactivity state is harmful to neurons in vivo in mice with prion neurodegeneration. Critically, targeting this signaling exclusively in astrocytes during prion disease is alone sufficient to prevent neuronal loss and significantly prolongs survival. Thus, the astrocyte reactivity state resulting from UPR over-activation is a distinct pathogenic mechanism that can by itself be effectively targeted for neuroprotection.
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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 OpenQuestion graph.