ArticleHuman molecular genetics2008
Autophagy induced by Alexander disease-mutant GFAP accumulation is regulated by p38/MAPK and mTOR signaling pathways.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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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.
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Who cites it
95 citing papers in PubMed, 169 citations in OpenAlex.
- Article
- Progressive gait and motor deficits in a rat model of Alexander disease.Behavioural brain research · 2026Article
- Synergistic Effects of Glial Fibrillary Acidic Protein Mutation and Overexpression in the Pathogenesis of Alexander Disease.International journal of molecular sciences · 2026Article
- Starvation of leukemic cells enhances DNA damage-induced apoptosis in vitro via ROS/p38 MAPK and prevents leukemia progression in fasting xenograft mice.The Journal of biological chemistry · 2026Article
- Exploring the Role of Peripheral Macrophages in Glioma Progression: The Metabolic Significance of Cyclooxygenase-2 (COX-2).International journal of molecular sciences · 2025Article
- Genotype-Phenotype Association for 14Neurology. Genetics · 2025Article
- Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation.International journal of molecular sciences · 2025Article
- Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.Journal of translational medicine · 2025Review
- Autophagy in alzheimer disease pathogenesis and its therapeutic values.Autophagy reports · 2025Review
- Adult-onset deactivation of autophagy leads to loss of synapse homeostasis and cognitive impairment, with implications for alzheimer disease.Autophagy · 2024Article
- GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients-A Pilot Study.International journal of molecular sciences · 2024Article
- Autophagy in neural stem cells and glia for brain health and diseases.Neural regeneration research · 2024Review
- Induced pluripotent stem cell-based assays recapture multiple properties of human astrocytes.Journal of cellular and molecular medicine · 2024Article
- Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control.Cell death & disease · 2024Article
- Alexander disease: the road ahead.Neural regeneration research · 2023Review
- STAT3 Drives GFAP Accumulation and Astrocyte Pathology in a Mouse Model of Alexander Disease.Cells · 2023Article
- Parkinsonism in Genetic Neurodevelopmental Disorders: A Systematic Review.Movement disorders clinical practice · 2023Review
- Identification of association fibers using ex vivo diffusion tractography in Alexander disease brains.Journal of neuroimaging : official journal of the American Society of Neuroimaging · 2022Article
- The role of astrocyte structural plasticity in regulating neural circuit function and behavior.Glia · 2022Review
- Effects of Alexander disease-associated mutations on the assembly and organization of GFAP intermediate filaments.Molecular biology of the cell · 2022Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Glial fibrillary acidic protein (GFAP) is the principle intermediate filament (IF) protein in astrocytes. Mutations in the GFAP gene lead to Alexander disease (AxD), a rare, fatal neurological disorder characterized by the presence of abnormal astrocytes that contain GFAP protein aggregates, termed Rosenthal fibers (RFs), and the loss of myelin. All GFAP mutations cause the same histopathological defect, i.e. RFs, though little is known how the mutations affect protein accumulation as well as astrocyte function. In this study, we found that GFAP accumulation induces macroautophagy, a key clearance mechanism for prevention of aggregated proteins. This autophagic response is negatively regulated by mammalian target of rapamycin (mTOR). The activation of p38 MAPK by GFAP accumulation is in part responsible for the down-regulation of phosphorylated-mTOR and the subsequent activation of autophagy. Our study suggests that AxD mutant GFAP accumulation stimulates autophagy, in a manner regulated by p38 MAPK and mTOR signaling pathways. Autophagy, in turn, serves as a mechanism to reduce GFAP levels.
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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.