ArticleAging cell2024
The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration.
Article in Aging cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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
15 citing papers in PubMed.
- The role of ATF4 in neurons under mitochondrial stress.NAR genomics and bioinformatics · 2026Article
- p38β-mediated BiP phosphorylation drives stemness and chemoresistance by suppressing UPR activation in hepatocellular carcinoma.Nature communications · 2026Article
- The role of sleep disorders in orchestrating proteomic dysfunction and multi-morbidity.Molecular psychiatry · 2026Review
- Organelle regulation of ferroptosis after intracerebral hemorrhage.Redox biology · 2026Review
- Artificial intelligence-driven nano-enhanced stem cell therapy for neurodegenerative diseases: from rational design to clinical translation.Journal of nanobiotechnology · 2026Review
- Nrf2 overexpression reprograms neural stem cell fate: promoting neuronal differentiation and functional recovery post-ischemic stroke via suppression of the ROS/NF-κB axis.Journal of translational medicine · 2026Article
- The Yin-Yang of Stress and Senescence: Integrated Stress Response and SASP Crosstalk in Stem Cell Fate, Regeneration, and Disease.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2026Article
- The dual role of ATF4 in neurons: from stress adaptation to therapeutic intervention.Frontiers in molecular neuroscience · 2026Review
- Hallmarks of stem cell aging.Cell stem cell · 2025Review
- Optic Atrophy 1: The Conductor of Cellular Harmony and Age-Related Pathologies.Aging and disease · 2025Review
- Review
- Aging of neural stem cells and vascular dysfunction: mechanisms, interconnection, and therapeutic perspectives.Cerebral circulation - cognition and behavior · 2025Review
- Mitochondrial Dynamics Drive Muscle Stem Cell Progression from Quiescence to Myogenic Differentiation.Cells · 2024Review
- The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration.Aging cell · 2024Article
- Investigating hormesis, aging, and neurodegeneration: From bench to clinics.Open medicine (Warsaw, Poland) · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress. ATF4 knockdown in Opa1-deficient NSCs accelerates cell death, while the increased expression of ATF4 enhances proliferation and survival. Using a Slc7a11 mutant, an ATF4 target, we show that ATF4-mediated glutathione production plays a critical role in maintaining NSC survival and function under stress conditions. Together, we show that the activation of the integrated stress response (ISR) pathway enables NSCs to adapt to metabolic stress due to mitochondrial dysfunction and metabolic stress and may serve as a therapeutic target to enhance NSC survival and function in aging and 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.