ArticleeLife2019
Site-specific phosphorylation and caspase cleavage of GFAP are new markers of Alexander disease severity.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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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.
The trial behind it
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Who cites it
39 citing papers in PubMed, 69 citations in OpenAlex.
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Alexander disease mutations differentially sensitize glial fibrillary acidic protein (GFAP) to posttranslational modifications and network disruption by oxidants.Redox biology · 2026Article
- GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.Acta neuropathologica communications · 2026Article
- The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression.Molecular neurobiology · 2025Review
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Article
- Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD.Neurology international · 2025Review
- Genotype-Phenotype Association for 14Neurology. Genetics · 2025Article
- The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.Journal of neurochemistry · 2025Review
- Article
- Morphological Characteristics and Extracellular Matrix Abnormalities in Astrocytes Derived From iPSCs of Children With Alexander Disease.CNS neuroscience & therapeutics · 2025Article
- Establishment and Use of Primary Cultured Astrocytes from Alexander Disease Model Mice.International journal of molecular sciences · 2024Article
- Induced pluripotent stem cell-based assays recapture multiple properties of human astrocytes.Journal of cellular and molecular medicine · 2024Article
- Characterization of the MT-2 Treg-like cell line in the presence and absence of forkhead box P3 (FOXP3).Immunology and cell biology · 2024Article
- Novel Approaches to Studying SLC13A5 Disease.Metabolites · 2024Review
- Glial fibrillary acidic protein in Alzheimer's disease: a narrative review.Brain communications · 2024Review
- Nonsense Variant PRDM16-Q187X Causes Impaired Myocardial Development and TGF-β Signaling Resulting in Noncompaction Cardiomyopathy in Humans and Mice.Circulation. Heart failure · 2023Article
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.eLife · 2023Article
- Alexander disease: the road ahead.Neural regeneration research · 2023Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Alexander disease (AxD) is a fatal neurodegenerative disorder caused by mutations in glial fibrillary acidic protein (GFAP), which supports the structural integrity of astrocytes. Over 70 GFAP missense mutations cause AxD, but the mechanism linking different mutations to disease-relevant phenotypes remains unknown. We used AxD patient brain tissue and induced pluripotent stem cell (iPSC)-derived astrocytes to investigate the hypothesis that AxD-causing mutations perturb key post-translational modifications (PTMs) on GFAP. Our findings reveal selective phosphorylation of GFAP-Ser13 in patients who died young, independently of the mutation they carried. AxD iPSC-astrocytes accumulated pSer13-GFAP in cytoplasmic aggregates within deep nuclear invaginations, resembling the hallmark Rosenthal fibers observed in vivo. Ser13 phosphorylation facilitated GFAP aggregation and was associated with increased GFAP proteolysis by caspase-6. Furthermore, caspase-6 was selectively expressed in young AxD patients, and correlated with the presence of cleaved GFAP. We reveal a novel PTM signature linking different GFAP mutations in infantile AxD.
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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.