ArticleProceedings of the National Academy of Sciences of the United States of America2023
Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 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
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- The impact of physical exercise on neuroinflammation mechanism in Alzheimer's disease.Frontiers in aging neuroscience · 2024Pooled it
- Epiregulin Mitigates Type 2 Diabetes-associated Cognitive Dysfunction by Inhibiting Hippocampal Neuronal Ferroptosis via the Nrf2 Pathway.Molecular neurobiology · 2026Article
- Gm26550 Modulates Learning and Memory by Increasing IGF1 mRNA Expression and Stability in Nrf2Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lineage-specific Nrf2 signaling orchestrates distinct neuroprotective mechanisms in acute ischemic stroke.Cell death & disease · 2026Article
- The histone demethylase KDM5C aggravates titanium particle-induced osteolysis by promoting macrophage inflammation and osteoclastogenesis.Cellular and molecular life sciences : CMLS · 2026Article
- HDAC7 acts as an astrocytic mediator of Aβ pathology that directly engages IKK to drive astrocyte neurotoxicity and neurodegeneration in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- The Role of Nuclear Factor Erythroid 2-Related Factor 2 in the Crosstalk Between Oxidative Stress and M1/M2 Microglial Polarization Following Ischemic Stroke.Molecular neurobiology · 2026Review
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
- Targeting central immune signaling enhances the effects of methylphenidate in alleviating apathy-like behavior in 5xFAD mice.Scientific reports · 2026Article
- Beyond the neuron: Exosomes as intercellular modulators of mitochondrial networks in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- RIP1 Exacerbates BBB Disruption by Impairing Autophagy-Mediated A2 Astrocyte Polarization in Hypertension-Induced Cerebral Microhemorrhage in Mice.Neurochemical research · 2026Article
- Ironing out mechanisms of ferroptotic death to tailor new stroke therapies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Targeting Reactive Astrocytes with Flavonoids to Alleviate Neuroinflammation and Promote Synaptic Function.Molecular neurobiology · 2026Review
- Early astrocyte-targeted intervention guided byEuropean journal of nuclear medicine and molecular imaging · 2026Article
- Neuroinflammation in Alzheimer's disease-associated sensory dysfunction: mechanistic links, actionable targets and therapeutic strategies.Frontiers in aging neuroscience · 2026Review
- Exercise-induced modulation of astrocyte in Alzheimer's disease: mechanisms and therapeutic implications.Frontiers in physiology · 2026Review
- Hyperbaric oxygen preconditioning alleviates spinal cord injury by inhibiting pro-inflammatory astrocyte polarization in a rat model of decompression sickness.Frontiers in immunology · 2026Article
- The emerging role of astrocytes in spatial cognition, action and Alzheimer's disease.Frontiers in cellular neuroscience · 2026Review
- Discovery of a novel Nrf2 activator that modulates mitochondrial function in neurons by regulating DHRS3-Nrf2 interaction after ischemic stroke.Theranostics · 2026Article
- Stage-Dependent Function of Astrocytes in Alzheimer's Disease: A Review.Neuroscience insights · 2026Review
4 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
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer's disease (AD). Neuroinflammation is induced by dysregulated glial activation, and astrocytes, the most abundant glial cells, become reactive upon neuroinflammatory cytokines released from microglia and actively contribute to neuronal loss. Therefore, blocking reactive astrocyte functions is a viable strategy to manage neurodegenerative disorders. However, factors or therapeutics directly regulating astrocyte subtypes remain unexplored. Here, we identified transcription factor NF-E2-related factor 2 (Nrf2) as a therapeutic target in neurotoxic reactive astrocytes upon neuroinflammation. We found that the absence of Nrf2 promoted the activation of reactive astrocytes in the brain tissue samples obtained from AD model 5xFAD mice, whereas enhanced Nrf2 expression blocked the induction of reactive astrocyte gene expression by counteracting NF-κB subunit p65 recruitment. Neuroinflammatory astrocytes robustly up-regulated genes associated with type I interferon and the antigen-presenting pathway, which were suppressed by Nrf2 pathway activation. Moreover, impaired cognitive behaviors observed in AD mice were rescued upon ALGERNON2 treatment, which potentiated the Nrf2 pathway and reduced the induction of neurotoxic reactive astrocytes. Thus, we highlight the potential of astrocyte-targeting therapy by promoting the Nrf2 pathway signaling for neuroinflammation-triggered neurodegeneration.
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.