ArticleNature aging2025
Modulating mTOR-dependent astrocyte substate transitions to alleviate neurodegeneration.
Article in Nature aging, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
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Who cites it
27 citing papers in PubMed.
- EGCG-loaded nanoparticles attenuate post-SAH white matter injury by targeting HO-1/S100A10 to suppress oxidative stress-induced reactive astrocytes.Redox report : communications in free radical research · 2026Article
- Review
- Thiol-Based Neuroprotective Copolymers Acutely Restore Redox Metabolism and Mediate Vasogenic Edema in a Mouse Model of Traumatic Brain Injury.Macromolecular bioscience · 2026Article
- Systemic epigenetic dysregulation as a driver of ageing and a therapeutic target.Nature reviews. Molecular cell biology · 2026Review
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- 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
- Single-cell Transcriptomics Reveals that the SORBS1/FBXO22/BAG3 Axis Drives Astrocyte Senescence via Calcium Signaling and Affects Alzheimer's Disease-Related Neuronal Damage.Neuromolecular medicine · 2026Article
- PINK1/Parkin-dependent mitophagy mediates astrocytic inflammatory responses to mitochondrial damage.bioRxiv : the preprint server for biology · 2026Article
- Engineered Exosomes: Innovative Strategies for Precision Drug Delivery in Parkinson's Disease.Molecular neurobiology · 2026Review
- Targeting the Microglia-Astrocyte OSM-OSMR Axis Restores Blood-Brain Barrier Integrity After Experimental Cerebral Ischemia-Reperfusion in Mice.Molecular neurobiology · 2026Article
- Differences of Gradient Connectivity and Ventricle Volumes in Long-Term Sensorineural Hearing Loss Related Cognitive Impairment Correlate With Transcriptional Signatures.Human brain mapping · 2026Article
- Astrocytes Control Norepinephrine Signaling in the Brain.Neuroscience bulletin · 2026Article
- Expression Patterns of T-Cell Intracellular Antigen 1 in Neurodegenerative Disorders and Stroke.International journal of molecular sciences · 2026Review
- USP11-PGAM5 Axis Promotes Neurotoxic Astrocyte Reactivity by Aggravating the mtDNA-cGAS-STING Pathway After Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microglia-astrocyte crosstalk as a key organizing principle of Alzheimer's disease: from homeostatic cooperation to maladaptive signaling loops.Frontiers in aging neuroscience · 2026Review
- Regulatory mechanisms and research progress of astrocytes in the neuro-endocrine-immune network.Frontiers in human neuroscience · 2026Review
- Ferroptosis in Parkinson's disease: a review of molecular mechanisms and emerging therapeutic strategies.Frontiers in neuroscience · 2026Review
- Promoting astrocyte-neuron triiodothyronine shuttling attenuates brain damage in neonatal hypoxic-ischemic encephalopathy.Journal of neuroinflammation · 2025Article
- VEGFR-3 deficiency in astrocytes exacerbates Japanese encephalitis virus-induced neuroinflammation in mouse brains.Zoological research · 2025Article
- Astrocyte diversity and subtypes: aligning transcriptomics with multimodal perspectives.EMBO reports · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Traditional approaches to studying astrocyte heterogeneity have mostly focused on analyzing static properties, failing to identify whether subtypes represent intermediate or final states of reactive astrocytes. Here we show that previously proposed neuroprotective and neurotoxic astrocytes are transitional states rather than distinct subtypes, as revealed through time-series multiomic sequencing. Neuroprotective astrocytes are an intermediate state of the transition from a nonreactive to a neurotoxic state in response to neuroinflammation, a process regulated by the mTOR signaling pathway. In Alzheimer's disease (AD) and aging, we observed an imbalance in neurotoxic and neuroprotective astrocytes in animal models and human patients. Moreover, targeting mTOR in astrocytes with rapamycin or shRNA mitigated astrocyte neurotoxic effects in neurodegenerative mouse models. Overall, our study uncovers a mechanism through which astrocytes exhibit neuroprotective functions before becoming neurotoxic under neuroinflammatory conditions and highlights mTOR modulation specifically in astrocytes as a potential therapeutic strategy for neurodegenerative diseases.
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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.