ArticleNeuron2025
A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.
Article in Neuron, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
50 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- Microglia activation by derepression of endogenous retroviruses drives inflammation and cellular senescence.Nature neuroscience · 2026Article
- Beyond neurons: Impact of cannabidiol on glial cells in ischemic stroke.Neural regeneration research · 2026Article
- Border-Associated Macrophage Migrasomes in Alzheimer's Disease: An Emerging Aβ-Senescence-Microglia Axis?Cells · 2026Review
- IL-33/ST2 Signaling and Microglial Functional-State Transitions After Spinal Cord Injury: Direct Evidence and Mechanistic Hypotheses.International journal of molecular sciences · 2026Review
- Neonatal small extracellular vesicle-loaded GelNB hydrogel reprograms the vascular-immune microenvironment for spinal cord injury repair.Bioactive materials · 2026Article
- Sex differences in the effects of chronic stress and oxycodone associative learning on glial markers in rat hippocampus.Neuroscience · 2026Article
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
- Mitochondrial stress response drives microglial senescence.Nature neuroscience · 2026Article
- The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence.Nature neuroscience · 2026Article
- Allosteric disordering of eIF2B regulates the integrated stress response.Nature chemical biology · 2026Article
- Review
- Butyrate-producing gut bacteria restrain PBAT microplastic-triggered brain microglial lipotoxicity via a microbiota-butyrate-mTORC1-ISR relay along the gut-brain axis.Journal of neuroinflammation · 2026Article
- Axonopathy: mechanisms and potential therapeutic targets for neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Persistent microglial activation following neonatal CMV infection mediates neurodegeneration.Science advances · 2026Article
- Neuro-Dynamic Quantitative Systems Pharmacology (QSP) model describing Alzheimer's disease pathophysiology and treatment effects.NPJ systems biology and applications · 2026Article
- The C3-C3aR axis drives rotenone-induced cognitive damage via synaptic engulfment, dark microglia and PANoptosis.Redox biology · 2026Article
- Cellular mechanisms of brain lipid metabolism in health and disease.Nature cell biology · 2026Review
- Integrated Stress Response Signatures Drive Monocyte Dysfunction in GBA1- and LRRK2-Linked Parkinson's Disease.Research square · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors.
Funding
Abstract
The brain's primary immune cells, microglia, are a leading causal cell type in Alzheimer's disease (AD). Yet, the mechanisms by which microglia can drive neurodegeneration remain unresolved. Here, we discover that a conserved stress signaling pathway, the integrated stress response (ISR), characterizes a microglia subset with neurodegenerative outcomes. Autonomous activation of ISR in microglia is sufficient to induce early features of the ultrastructurally distinct "dark microglia" linked to pathological synapse loss. In AD models, microglial ISR activation exacerbates neurodegenerative pathologies and synapse loss while its inhibition ameliorates them. Mechanistically, we present evidence that ISR activation promotes the secretion of toxic lipids by microglia, impairing neuron homeostasis and survival in vitro. Accordingly, pharmacological inhibition of ISR or lipid synthesis mitigates synapse loss in AD models. Our results demonstrate that microglial ISR activation represents a neurodegenerative phenotype, which may be sustained, at least in part, by the secretion of toxic lipids.
Indexed as
Identifiers
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.