Affinage

GFAP

Glial fibrillary acidic protein · UniProt P14136

Round 2 corrected
Length
432 aa
Mass
49.9 kDa
Annotated
2026-04-28
130 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GFAP is the principal type III intermediate filament protein of astrocytes, serving as the structural backbone of the astrocyte cytoskeleton and a critical regulator of astrocyte–neuron interactions, cell morphology, and extracellular matrix adhesion. Its polymerization is directly inhibited by Ca²⁺-dependent S100 protein binding and modulated by alphaB-crystallin, while palmitoylation at Cys-291 (reversed by PPT1) regulates astrocyte proliferation and gliosis (PMID:7918670, PMID:19129171, PMID:33753498). Transcription of GFAP is controlled by cooperative promoter elements (NFI, SP1, STAT3, NF-κB) and epigenetic mechanisms including DNA methylation, histone acetylation, and MeCP2 binding, and is induced by TGF-β1/Smad–MAPK/PI3K signaling downstream of glutamate (PMID:23832770, PMID:18419760, PMID:24269336, PMID:29852171). Dominant missense mutations in GFAP cause Alexander disease through protein aggregation into Rosenthal fibers, impaired vesicle trafficking and ATP secretion, disrupted organelle distribution, and reduced proteasomal function (PMID:11138011, PMID:30355500, PMID:19146851).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1994 High

    Establishing the first direct mechanism regulating GFAP filament dynamics: S100 protein was shown to inhibit GFAP polymerization in a Ca²⁺-dependent manner, identifying an assembly checkpoint responsive to intracellular calcium.

    Evidence In vitro sedimentation and viscometry polymerization assays with purified proteins

    PMID:7918670

    Open questions at the time
    • Identity of the specific S100 family member(s) acting in vivo not resolved
    • Whether other intermediate filament-associated proteins compete with S100 for GFAP binding is unknown
  2. 1996 High

    GFAP was shown to be required for normal astrocyte–neuron communication: GFAP-null mice had severely reduced astrocyte intermediate filaments and enhanced hippocampal LTP, demonstrating that GFAP constrains synaptic plasticity.

    Evidence Gene-targeted knockout mouse with electrophysiological recording in hippocampal slices

    PMID:8692820

    Open questions at the time
    • Mechanism by which GFAP loss enhances LTP (gliotransmitter release, K⁺ buffering, structural support) was not determined
    • Whether other intermediate filaments (vimentin) partially compensate was not addressed
  3. 1998 High

    Excess wild-type GFAP was shown to be sufficient to cause astrocyte pathology: transgenic GFAP-overexpressing mice formed Rosenthal fiber inclusions identical to those in Alexander disease and developed fatal encephalopathy, establishing a dose-dependent gain-of-function mechanism.

    Evidence Transgenic mouse overexpression with histological and immunohistochemical analysis

    PMID:9466565

    Open questions at the time
    • Threshold of GFAP overexpression required to trigger pathology not quantified
    • Whether Rosenthal fibers are directly toxic or markers of a broader proteostatic failure was unresolved
  4. 1998 Medium

    TGF-β1 was identified as a key transcriptional inducer of GFAP, counteracted by FGF-2 through tyrosine kinase signaling in a protein-synthesis-dependent manner, establishing growth factor cross-talk in GFAP regulation.

    Evidence Astrocyte culture with northern/western blot, pharmacological inhibition, cycloheximide chase

    PMID:9537840

    Open questions at the time
    • Identity of the protein whose new synthesis is required for FGF-2-mediated repression was not established
    • Whether this cross-talk operates in vivo during injury responses is untested
  5. 2001 High

    Dominant missense mutations in GFAP were identified as the cause of Alexander disease — the first Mendelian astrocyte disorder traced to a single gene — directly linking GFAP sequence variants to Rosenthal fiber formation.

    Evidence DNA sequencing of patient cohorts with cellular transfection validation

    PMID:11138011

    Open questions at the time
    • How individual mutations alter GFAP filament assembly at the structural level was not resolved
    • Genotype–phenotype correlations for severity and onset age were incomplete
  6. 2005 High

    Expansion of the Alexander disease mutation catalog across infantile, juvenile, and adult forms confirmed a consistent gain-of-function mechanism for all pathogenic GFAP variants.

    Evidence Multi-center patient cohort sequencing with cellular transfection assays

    PMID:15732097

    Open questions at the time
    • Whether different mutations activate distinct downstream stress pathways was not addressed
  7. 2008 Medium

    The signaling cascade upstream of GFAP transcriptional induction was elaborated: glutamate activates the GFAP promoter through mGluR2/3-mediated TGF-β1 secretion, Smad-2 nuclear translocation, and cooperative MAPK/ERK and PI3K pathway engagement.

    Evidence GFAP-lacZ reporter astrocytes with neutralizing antibodies and pathway-specific pharmacological inhibitors

    PMID:18419760

    Open questions at the time
    • Whether Smad and MAPK/PI3K signals converge on the same promoter elements or act on distinct cis-elements not determined
    • Contribution of this pathway relative to other injury signals in vivo is unknown
  8. 2008 Medium

    Both excess wild-type and mutant GFAP were shown to impair proteasomal function and decrease cell proliferation in primary astrocytes, identifying proteostatic collapse as a central feature of GFAP toxicity in Alexander disease.

    Evidence Primary astrocyte cultures from transgenic and knock-in AxD mouse models with proteasome activity and cell death assays

    PMID:19146851

    Open questions at the time
    • Whether proteasome impairment is a direct effect of GFAP aggregates or secondary to sequestration of proteasome regulators is unclear
    • Relative contribution of impaired autophagy vs. proteasome dysfunction not dissected
  9. 2009 High

    alphaB-crystallin was established as an astrocyte-specific suppressor of GFAP toxicity: its genetic elevation rescued AxD mouse models from seizures and restored glutamate transporter expression, while its loss exacerbated mortality.

    Evidence Epistatic genetic crosses (GFAP-overexpressor × Cryab-null; AxD knock-in × Cryab-transgenic) with survival, IHC, and western blot

    PMID:19129171

    Open questions at the time
    • Mechanism of Cryab action (direct chaperone activity on GFAP filaments vs. aggregate clearance) not resolved
    • Whether Cryab restoration is therapeutically viable in humans is untested
  10. 2013 Medium

    Cooperative transcription factor architecture of the GFAP promoter was mapped in vivo: NFI, SP1, STAT3, and NF-κB sites each contribute to promoter strength and astrocyte specificity, with a cooperative B-region spanning four contiguous elements.

    Evidence Transgenic mice with block-mutant and site-specific mutant GFAP-reporter constructs

    PMID:23832770

    Open questions at the time
    • Which factor combinations are essential versus modulatory in different brain regions is not resolved
    • Chromatin context and 3D promoter architecture were not examined
  11. 2013 Medium

    Epigenetic regulation of GFAP was demonstrated through MeCP2 binding to the methylated GFAP promoter; MeCP2 knockdown in vivo increased GFAP expression in a sex-specific manner, revealing a layer of epigenetic control.

    Evidence In vivo siRNA knockdown in neonatal rat amygdala and hypothalamus with RT-qPCR and western blot

    PMID:24269336

    Open questions at the time
    • Molecular basis of the sex-specific effect is unknown
    • Relationship to MeCP2 loss in Rett syndrome pathology not explored
  12. 2014 Medium

    GFAP isoforms (α and δ) were shown to exert distinct functions: GFAP-α knockdown altered integrin expression and cell motility, while pan-GFAP knockdown drastically increased laminin adhesion, demonstrating isoform-specific regulation of astrocyte–ECM interactions.

    Evidence shRNA-mediated isoform-specific knockdown with motility, adhesion, integrin, and ECM protein analysis in astrocytoma cells

    PMID:24696300

    Open questions at the time
    • Whether these isoform-specific ECM effects operate in primary astrocytes and in vivo is untested
    • Direct binding partners that distinguish the isoforms at the ECM interface are unknown
  13. 2016 Medium

    FRAP experiments revealed that GFAPδ exchanges more slowly than GFAPα within the filament network and that GFAPδ-induced network collapse alters focal adhesion size, linking isoform dynamics to cytoskeletal mechanotransduction.

    Evidence Fluorescence recovery after photobleaching and focal adhesion analysis in astrocytoma cells

    PMID:27141937

    Open questions at the time
    • Whether altered exchange kinetics are due to intrinsic assembly differences or differential partner interactions is unclear
    • Relevance of GFAPδ network collapse to in vivo astrocyte morphology not established
  14. 2018 High

    Alexander disease mutations in GFAP were shown in a human iPSC model to disrupt organelle distribution (ER and lysosomes perinuclear redistribution), impair ATP secretion, and attenuate calcium wave propagation, identifying vesicle trafficking and secretory function as primary cellular deficits.

    Evidence Patient-derived iPSC astrocytes with CRISPR/Cas9 isogenic correction, organelle imaging, ATP release assay, calcium imaging

    PMID:30355500

    Open questions at the time
    • Whether organelle redistribution is a direct mechanical consequence of GFAP aggregation or mediated by motor protein dysfunction is unknown
    • Contribution of impaired ATP release to non-cell-autonomous neuronal damage not quantified
  15. 2018 Medium

    Thyroid hormone was shown to regulate GFAP expression through coordinated DNA methylation and histone acetylation at the GFAP promoter, with maternal hypothyroidism causing epigenetic silencing reversible by hormone supplementation.

    Evidence Rat hypothyroidism model with bisulfite sequencing, ChIP, HDAC activity assay, and hormone rescue

    PMID:29852171

    Open questions at the time
    • Which DNA methyltransferases and HDACs are directly recruited to the GFAP promoter in this context is not identified
    • Whether this contributes to neurodevelopmental deficits of congenital hypothyroidism is speculative
  16. 2021 High

    Palmitoylation at Cys-291 was identified as a post-translational modification that regulates GFAP function: hyperpalmitoylation (as in PPT1 deficiency) promotes astrocyte proliferation and gliosis, while a C291A knock-in attenuates neurodegeneration, revealing a lipid modification switch on GFAP.

    Evidence Palm-proteomics, in vitro palmitoylation assay, C291A knock-in mouse, cell proliferation assay

    PMID:33753498

    Open questions at the time
    • The palmitoltransferase(s) that modify Cys-291 are not identified
    • How palmitoylation alters GFAP filament assembly or protein–protein interactions at the molecular level is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions remain: the structural basis by which individual Alexander disease mutations alter GFAP assembly, the identity of the palmitoltransferase modifying Cys-291, the mechanism linking GFAP aggregation to organelle redistribution and proteasome impairment, and whether alphaB-crystallin-based strategies can be translated therapeutically.
  • No high-resolution structural model of pathogenic GFAP filament assembly exists
  • Causal chain from GFAP aggregation to proteasome impairment versus autophagy dysfunction not dissected
  • Therapeutic window for Cryab or depalmitoylation strategies in Alexander disease unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 4 GO:0005829 cytosol 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 2
Partners
CRYABPPT1S100BVIM

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GFAP-null mice (generated by gene targeting in embryonic stem cells) showed severely reduced intermediate filaments in astrocytes and exhibited enhanced long-term potentiation (both population spike amplitude and EPSP slope) in the CA1 hippocampal region compared to controls, demonstrating that GFAP is required for normal astrocyte-neuronal interactions that modulate synaptic efficacy. Gene targeting (knockout mouse), electrophysiological recording of LTP in hippocampal slices Proceedings of the National Academy of Sciences of the United States of America High 8692820
1994 S100 protein (a Ca2+-binding protein) binds directly to GFAP and inhibits its polymerization in a Ca2+-dependent manner: it interferes with nucleation and polymer growth, reduces the rate and extent of GFAP assembly, increases the critical concentration for assembly, and disassembles preformed glial filaments, suggesting S100 regulates glial filament dynamics in response to elevated intracellular Ca2+. Sedimentation assay, viscometry, in vitro polymerization assay Biochimica et biophysica acta High 7918670
2001 Dominant missense mutations in the coding region of GFAP cause Alexander disease, establishing GFAP as the first identified gene whose primary mutation causes an astrocyte disorder; mutant GFAP leads to formation of Rosenthal fiber inclusions in astrocytes. DNA sequence analysis of patient samples, cellular transfection assays with mutant constructs Nature genetics High 11138011
1998 Transgenic mice overexpressing human GFAP develop astrocyte hypertrophy, upregulate small heat-shock proteins, and form cytoplasmic inclusion bodies (Rosenthal fibers) identical to those in Alexander disease, resulting in fatal encephalopathy; this established that elevated GFAP levels per se alter astrocyte function and cause pathology. Transgenic mouse overexpression, histological and immunohistochemical analysis The American journal of pathology High 9466565
2009 alphaB-crystallin (Cryab) regulates GFAP assembly and suppresses GFAP toxicity in Alexander disease mouse models: loss of Cryab increased mortality in GFAP-overexpressing mice, while transgenic elevation of Cryab rescued animals from terminal seizures, restored glutamate transporter Glt1 (EAAT2) expression, and reduced the CNS stress response, demonstrating an astrocyte-specific protective mechanism. Genetic crosses of mouse models (GFAP overexpressor × Cryab-null; AxD mutation knock-in × Cryab transgenic), survival analysis, immunohistochemistry, western blot Human molecular genetics High 19129171
2021 GFAP is palmitoylated in vitro and in vivo, with cysteine-291 identified as the unique palmitoylation site; PPT1 depalmitoylates GFAP. Hyperpalmitoylated GFAP promotes astrocyte proliferation, and in PPT1-deficient mice elevated palmitoylated GFAP accelerates astrogliosis. Mutation of Cys-291 to Ala attenuates astrogliosis and concurrent neurodegenerative pathology in PPT1-knockin mice. Palm-proteomics, in vitro palmitoylation assay, site-directed mutagenesis (C291A knock-in), cell proliferation assay, in vivo mouse model Proceedings of the National Academy of Sciences of the United States of America High 33753498
2016 GFAPδ and GFAPα isoforms differ in their exchange dynamics within the intermediate filament network: FRAP experiments showed GFP-GFAPδ exchanges significantly more slowly than GFP-GFAPα; GFAPδ-induced network collapse further decreased recovery of both isoforms and altered cell morphology and focal adhesion size without affecting migration or proliferation. Fluorescence recovery after photobleaching (FRAP), live-cell imaging, focal adhesion analysis in astrocytoma cells Cellular and molecular life sciences : CMLS Medium 27141937
2014 Isoform-specific silencing of GFAPα (canonical) in astrocytoma cells shifted the GFAPδ:GFAPα ratio, leading to changes in integrin expression, decreased plectin, increased laminin, and significantly decreased cell motility. Pan-GFAP knockdown caused decreased cell spreading, increased integrin expression, and >100-fold increased adhesion to laminin, demonstrating distinct isoform-specific roles of GFAP in regulating astrocyte–extracellular matrix interactions. shRNA-mediated isoform-specific knockdown, cell motility assay, adhesion assay, integrin and ECM protein analysis FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 24696300
2014 Histone deacetylase (HDAC) inhibition (trichostatin A or sodium butyrate) reduced GFAP transcription in human astrocytes and astrocytoma cells, and the reduced transcription increased the GFAPδ:GFAPα ratio by promoting alternative splicing dependent on SR protein splicing factors; HDAC inhibition also caused GFAP network aggregation similar to GFAPδ-induced network collapse. HDAC inhibitor treatment, RT-qPCR, western blot, immunofluorescence, splicing factor analysis in primary human astrocytes and astrocytoma cells Journal of cell science Medium 25128567
2018 AxD patient-derived iPSC astrocytes carrying GFAP mutations (corrected by gene editing as isogenic controls) displayed GFAP aggregates, perinuclear redistribution of ER and lysosomes, impaired extracellular ATP release, and attenuated calcium wave propagation, demonstrating that AxD mutations in GFAP disrupt intracellular vesicle regulation and astrocyte secretory function. iPSC derivation from AxD patients, CRISPR/Cas9 isogenic correction, RNA-seq, organelle imaging, ATP release assay, calcium imaging Cell reports High 30355500
2008 Primary astrocytes from Alexander disease mouse models (GFAP overexpressor transgenic and AxD-mutation knock-in) showed that both mutant GFAP and excess wild-type GFAP promote cytoplasmic inclusion formation, disrupt the cytoskeleton, decrease cell proliferation, increase cell death, reduce proteasomal function, and compromise stress resistance. Primary astrocyte culture from transgenic and knock-in mice, immunocytochemistry, cell proliferation and death assays, proteasome activity assay Experimental cell research Medium 19146851
2008 Glutamate activates the GFAP gene promoter in cortical astrocytes via metabotropic glutamate receptors (blocked by mGluR2/3 antagonist MCPG) and is mediated by TGF-β1 secretion, leading to Smad-2 nuclear translocation and requiring cooperative activation of both MAPK/ERK and PI3K pathways alongside the canonical TGF-β/Smad pathway. Transgenic GFAP-lacZ reporter astrocytes, neutralizing antibodies, pharmacological inhibitors (MCPG, PD98059, LY294002), Smad nuclear translocation assay Journal of neurochemistry Medium 18419760
2005 Mutant GFAP behavior in cellular transfection assays confirmed that pathogenic Alexander disease mutations produce a gain-of-function leading to Rosenthal fiber formation, and expanded the catalog of causative mutations across infantile, juvenile, and adult forms of the disease. DNA sequencing of patient cohorts, cellular transfection assays Annals of neurology High 15732097
2000 TNF-α treatment of cultured astrocytes caused dramatic GFAP over-expression associated with substantial activation of MAPK Erk2; this over-expression was significantly attenuated by the MAPK inhibitor PD98059, placing TNF-α–MAPK signaling upstream of GFAP upregulation. Astrocyte cell culture, western blot, pharmacological MAPK inhibition (PD98059) Neuroreport Low 10674496
1998 TGF-β1 significantly increased GFAP mRNA and protein in cultured astrocytes without morphological change, while FGF-2 (acting through tyrosine kinase/FGFR autophosphorylation, blocked by 5′-methylthioadenosine) decreased GFAP mRNA and protein and also inhibited TGF-β1-mediated GFAP induction; cycloheximide blocked FGF-2 inhibition of TGF-β1-mediated GFAP mRNA increase only when both were applied together, indicating a protein-synthesis-dependent counter-regulatory mechanism. Astrocyte culture, northern blot, western blot, pharmacological inhibition, cycloheximide chase Glia Medium 9537840
2013 Alternative splicing of GFAP generates isoforms (GFAPα and GFAPδ) with distinct subcellular mRNA localization: a larger fraction of GFAPα mRNA localizes to astrocyte protrusions compared to GFAPδ mRNA, and this differential localization depends on the distinct 3′-exon sequences of each isoform. RT-qPCR, immunofluorescence, subcellular mRNA fractionation, fluorescence in situ hybridization in primary mouse astrocytes PloS one Medium 23991052
2013 MeCP2 binds to methylated regions of the GFAP promoter and suppresses GFAP expression; transient siRNA knockdown of MeCP2 in the neonatal rat amygdala and hypothalamus increased GFAP mRNA and protein specifically in females but not males, without altering other astrocyte markers (S100β, vimentin), demonstrating sex-specific epigenetic regulation of GFAP by MeCP2. In vivo siRNA knockdown, RT-qPCR, western blot, immunohistochemistry in rat brain Brain research Medium 24269336
2018 Maternal hypothyroidism causes epigenetic silencing of Gfap in developing neocortex via increased DNA methylation and decreased histone acetylation at the Gfap promoter, coupled with increased HDAC activity; thyroid hormone supplementation reversed these changes, demonstrating that thyroid hormone regulates GFAP transcription through coordinated DNA methylation and histone modification. Rat model of maternal hypothyroidism, bisulfite sequencing, ChIP for histone acetylation, HDAC activity assay, RT-qPCR, western blot Biochemical and biophysical research communications Medium 29852171
2013 Transgenic analysis identified NFI, SP1, STAT3, and NF-κB binding sites within the human GFAP promoter as important regulators of promoter strength and/or astrocyte specificity, while mutation of a conserved AP-1 site had little effect; mutation of the B region (bp -1612 to -1489) spanning four contiguous sequences cooperatively reduced transgene activity by ≥50% each, indicating that multiple sites contribute cooperatively to GFAP transcriptional regulation. Transgenic mice carrying block-mutant and site-specific mutant GFAP-reporter constructs, in vivo reporter expression analysis Glia Medium 23832770
2019 GFAP-null/Vimentin-null (GFAP−/−Vim−/−) double-knockout mice showed more pronounced memory extinction compared to wild-type in IntelliCage reversal learning tasks, while overall locomotion, learning in Morris water maze, and trace fear conditioning were comparable, indicating that the astrocyte intermediate filament system (GFAP + vimentin together) modulates hippocampal circuit reorganization underlying memory extinction. Double-knockout mice, open field, object recognition, Morris water maze, trace fear conditioning, IntelliCage reversal learning Biological chemistry Medium 31063456

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 GFAP in health and disease. Progress in neurobiology 844 21219963
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
1994 GFAP and astrogliosis. Brain pathology (Zurich, Switzerland) 735 7952264
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2015 Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system. Current opinion in cell biology 685 25726916
1985 Glial fibrillary acidic protein (GFAP): the major protein of glial intermediate filaments in differentiated astrocytes. Journal of neuroimmunology 673 2409105
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2001 Mutations in GFAP, encoding glial fibrillary acidic protein, are associated with Alexander disease. Nature genetics 547 11138011
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2015 Widespread macromolecular interaction perturbations in human genetic disorders. Cell 454 25910212
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1994 GFAP promoter directs astrocyte-specific expression in transgenic mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 430 8120611
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2016 Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury. JAMA neurology 394 27018834
1993 GFAP mRNA increases with age in rat and human brain. Neurobiology of aging 346 8247224
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2007 Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS genetics 325 17500595
2008 GFAP promoter elements required for region-specific and astrocyte-specific expression. Glia 315 18240313
2006 GFAP transgenic zebrafish. Gene expression patterns : GEP 302 16765104
1996 Targeted deletion in astrocyte intermediate filament (Gfap) alters neuronal physiology. Proceedings of the National Academy of Sciences of the United States of America 280 8692820
2010 GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology 277 21079180
2022 EWSR1-induced circNEIL3 promotes glioma progression and exosome-mediated macrophage immunosuppressive polarization via stabilizing IGF2BP3. Molecular cancer 257 35031058
2019 Glial Fibrillary Acidic Protein in Serum is Increased in Alzheimer's Disease and Correlates with Cognitive Impairment. Journal of Alzheimer's disease : JAD 257 30594925
2004 An investigation into the human serum "interactome". Electrophoresis 247 15174051
1989 Changes in brain gene expression shared by scrapie and Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 244 2780570
2021 Plasma glial fibrillary acidic protein detects Alzheimer pathology and predicts future conversion to Alzheimer dementia in patients with mild cognitive impairment. Alzheimer's research & therapy 229 33773595
2005 LIF and BMP signaling generate separate and discrete types of GFAP-expressing cells. Development (Cambridge, England) 223 16314487
2021 Beyond the GFAP-Astrocyte Protein Markers in the Brain. Biomolecules 212 34572572
2010 Chaperone-mediated autophagy: molecular mechanisms and physiological relevance. Seminars in cell & developmental biology 210 20176123
2023 GFAP as a Potential Biomarker for Alzheimer's Disease: A Systematic Review and Meta-Analysis. Cells 209 37174709
1998 Fatal encephalopathy with astrocyte inclusions in GFAP transgenic mice. The American journal of pathology 209 9466565
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2015 Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder. Neuroscience 202 26742791
2005 Glial fibrillary acidic protein mutations in infantile, juvenile, and adult forms of Alexander disease. Annals of neurology 202 15732097
2011 GFAP mutations, age at onset, and clinical subtypes in Alexander disease. Neurology 201 21917775
2014 Enteric GFAP expression and phosphorylation in Parkinson's disease. Journal of neurochemistry 152 24749759
1999 Glial fibrillary acidic protein (GFAP): modulation by growth factors and its implication in astrocyte differentiation. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 152 10412574
1994 Structure and transcriptional regulation of the GFAP gene. Brain pathology (Zurich, Switzerland) 138 7952266
2019 Clinical characteristics of autoimmune GFAP astrocytopathy. Journal of neuroimmunology 132 30991306
2003 Differential expression of GFAP in early v late AMD: a quantitative analysis. The British journal of ophthalmology 128 12928288
2017 Type III Intermediate Filaments Desmin, Glial Fibrillary Acidic Protein (GFAP), Vimentin, and Peripherin. Cold Spring Harbor perspectives in biology 109 29196434
2022 Association of plasma glial fibrillary acidic protein (GFAP) with neuroimaging of Alzheimer's disease and vascular pathology. Alzheimer's & dementia (Amsterdam, Netherlands) 102 35252538
2004 Expression specificity of GFAP transgenes. Neurochemical research 101 15662842
2022 Blocking C3d+/GFAP+ A1 Astrocyte Conversion with Semaglutide Attenuates Blood-Brain Barrier Disruption in Mice after Ischemic Stroke. Aging and disease 100 35656116
2021 Glial Fibrillary Acidic Protein (GFAP): Neuroinflammation Biomarker in Acute Ischemic Stroke. Journal of inflammation research 95 35002283
2020 GFAP at 50. ASN neuro 94 32811163
2021 Regulation of GFAP Expression. ASN neuro 93 33601918
2016 Assessment of Serum UCH-L1 and GFAP in Acute Stroke Patients. Scientific reports 92 27074724
2004 Non-invasive imaging of GFAP expression after neuronal damage in mice. Neuroscience letters 91 15331155
1998 Regulation of astrocyte GFAP expression by TGF-beta1 and FGF-2. Glia 91 9537840
2009 Suppression of GFAP toxicity by alphaB-crystallin in mouse models of Alexander disease. Human molecular genetics 88 19129171
1989 Two brain nuclei controlling circadian rhythms are identified by GFAP immunoreactivity in hamsters and rats. Neuroscience letters 86 2664580
2020 Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration. Journal of Alzheimer's disease : JAD 84 32804092
1998 Correlation of B-FABP and GFAP expression in malignant glioma. Oncogene 73 9591779
1984 Glial fibrillary acidic protein (GFAP) immunoreactivity in peripheral nerve sheath tumors. Ultrastructural pathology 70 6543600
2022 Neuroinflammation Is Associated with GFAP and sTREM2 Levels in Multiple Sclerosis. Biomolecules 67 35204724
2019 Importance of GFAP isoform-specific analyses in astrocytoma. Glia 66 30667110
1999 Neurons induce GFAP gene promoter of cultured astrocytes from transgenic mice. Glia 63 10384875
2019 Enteric Glia: S100, GFAP, and Beyond. Anatomical record (Hoboken, N.J. : 2007) 62 30951262
1985 Measurement of GFAP in hepatic encephalopathy by ELISA and transblots. Journal of neuropathology and experimental neurology 62 3897466
1996 GFAP Transgenic Mice. Methods (San Diego, Calif.) 61 8954847
1996 Repeated seizures increase GFAP and vimentin in the hippocampus. Brain research 60 8738264
2006 Astrocyte heterogeneity revealed by expression of a GFAP-LacZ transgene. Glia 57 16482522
2005 Olig2 expression, GFAP, p53 and 1p loss analysis contribute to glioma subclassification. Neuropathology and applied neurobiology 57 15634232
2014 Histone acetylation in astrocytes suppresses GFAP and stimulates a reorganization of the intermediate filament network. Journal of cell science 54 25128567
2008 Glutamate activates GFAP gene promoter from cultured astrocytes through TGF-beta1 pathways. Journal of neurochemistry 54 18419760
1989 Neuronal modulation of Schwann cell glial fibrillary acidic protein (GFAP). Journal of neuroscience research 54 2769798
2019 The role of GFAP and vimentin in learning and memory. Biological chemistry 53 31063456
2017 Circulating CD9+/GFAP+/survivin+ exosomes in malignant glioma patients following survivin vaccination. Oncotarget 52 29383115
2018 Mutations in GFAP Disrupt the Distribution and Function of Organelles in Human Astrocytes. Cell reports 50 30355500
2005 Expression of MBP, PLP, MAG, CNP, and GFAP in the Human Alcoholic Brain. Alcoholism, clinical and experimental research 50 16205370
2003 GFAP promoter drives Müller cell-specific expression in transgenic mice. Investigative ophthalmology & visual science 50 12882814
1994 Regional changes in expression of NCAM, GFAP, and S100 in aging rat brain. Neurobiology of aging 47 7824058
2024 Prediction of clinical progression in nervous system diseases: plasma glial fibrillary acidic protein (GFAP). European journal of medical research 46 38216970
2021 GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 46 33753498
1994 Mechanism of S100 protein-dependent inhibition of glial fibrillary acidic protein (GFAP) polymerization. Biochimica et biophysica acta 45 7918670
1990 Müller cell GFAP expression exhibits gradient from focus of photoreceptor light damage. Current eye research 44 2200639
2016 GFAP isoforms control intermediate filament network dynamics, cell morphology, and focal adhesions. Cellular and molecular life sciences : CMLS 43 27141937
2008 Properties of astrocytes cultured from GFAP over-expressing and GFAP mutant mice. Experimental cell research 42 19146851
2000 TNF-alpha induced over-expression of GFAP is associated with MAPKs. Neuroreport 42 10674496
1994 Normal and pathological expression of GFAP promoter elements in transgenic mice. Glia 40 7890332
2010 Drug screening to identify suppressors of GFAP expression. Human molecular genetics 39 20538881
1985 GFAP in brain tumor diagnosis: possibilities and limitations. Pathology, research and practice 39 4034433
2013 Transgenic analysis of GFAP promoter elements. Glia 37 23832770
1990 GFAP turnover during astroglial proliferation and differentiation. Brain research. Developmental brain research 37 2279327
2023 Hippocampal GFAP-positive astrocyte responses to amyloid and tau pathologies. Brain, behavior, and immunity 36 36878332
2015 Heterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency. Journal of neurochemistry 34 26118771
2015 CSF and Blood Levels of GFAP in Alexander Disease. eNeuro 34 26478912
2013 MeCP2 regulates GFAP expression within the developing brain. Brain research 33 24269336
2020 Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Annals of clinical and translational neurology 31 33047897
2014 Silencing GFAP isoforms in astrocytoma cells disturbs laminin-dependent motility and cell adhesion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 31 24696300
2022 Serum GFAP - reference interval and preanalytical properties in Danish adults. Clinical chemistry and laboratory medicine 30 36067832
2000 Alterations in levels of mRNAs coding for glial fibrillary acidic protein (GFAP) and vimentin genes in the central nervous system of hens treated with diisopropyl phosphorofluoridate (DFP). Neurochemical research 30 10943999
1986 Anaplasia and heterogeneity of GFAP expression in gliomas. Tumori 30 3705189
2014 Immunohistochemical analysis of GFAP-δ and nestin in cerebral astrocytomas. Brain tumor pathology 29 25178519
2021 Expression of GFAP and Tau Following Blast Exposure in the Cerebral Cortex of Ferrets. Journal of neuropathology and experimental neurology 27 33421075
2020 Encephalitis with radial perivascular emphasis: Not necessarily associated with GFAP antibodies. Neurology(R) neuroimmunology & neuroinflammation 27 32019875
2020 CSF levels of glutamine synthetase and GFAP to explore astrocytic damage in seronegative NMOSD. Journal of neurology, neurosurgery, and psychiatry 27 32217788
2012 Quantitative analysis of GFAP- and S100 protein-immunopositive astrocytes to investigate the severity of traumatic brain injury. Legal medicine (Tokyo, Japan) 27 22301378
2024 The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases. Journal of neurochemistry 26 39289040
2022 GFAP Alternative Splicing and the Relevance for Disease - A Focus on Diffuse Gliomas. ASN neuro 26 35673702
2020 Complex and regional-specific changes in the morphological complexity of GFAP+ astrocytes in middle-aged mice. Neurobiology of aging 26 33493951
2016 Effects of enriched environment on alterations in the prefrontal cortex GFAP- and S100B-immunopositive astrocytes and behavioral deficits in MK-801-treated rats. Neuroscience 26 27063100
2015 Striatal Injury with 6-OHDA Transiently Increases Cerebrospinal GFAP and S100B. Neural plasticity 26 26090233
1991 Schwann cell GFAP expression increases in axonal neuropathies. Journal of the neurological sciences 26 1649261
2016 Anorexia Reduces GFAP+ Cell Density in the Rat Hippocampus. Neural plasticity 25 27579183
2013 Alternative mRNA splicing from the glial fibrillary acidic protein (GFAP) gene generates isoforms with distinct subcellular mRNA localization patterns in astrocytes. PloS one 25 23991052
2013 GFAP expression and social deficits in transgenic mice overexpressing human sAPPα. Glia 24 23840007
2016 Asymmetric Distribution of GFAP in Glioma Multipotent Cells. PloS one 23 26953813
2011 Archetypal and new families with Alexander disease and novel mutations in GFAP. Archives of neurology 23 21987397
2019 Refining the concept of GFAP toxicity in Alexander disease. Journal of neurodevelopmental disorders 22 31838996
1997 Astrocyte activation by Sindbis virus: expression of GFAP, cytokines, and adhesion molecules. Glia 21 9097072
2024 GFAP-isoforms in the nervous system: Understanding the need for diversity. Current opinion in cell biology 20 38401182
2018 Mechanisms involved in epigenetic down-regulation of Gfap under maternal hypothyroidism. Biochemical and biophysical research communications 20 29852171
2023 Striatal spatial heterogeneity, clustering, and white matter association of GFAP+ astrocytes in a mouse model of Huntington's disease. Frontiers in cellular neuroscience 19 37187609
2022 Serum glial fibrillary acidic protein (GFAP) predicts outcome after intracerebral and subarachnoid hemorrhage. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 19 35896928
2017 Glial fibrillary acidic protein (GFAP) is a novel biomarker for the prediction of autoimmune diabetes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 19 28546444
1998 Effects of microgravity and bone morphogenetic protein II on GFAP in rat brain. Journal of applied physiology (Bethesda, Md. : 1985) 19 9688751
2022 Serological biomarkers in autoimmune GFAP astrocytopathy. Frontiers in immunology 18 35983033
2010 Glial cells revealed by GFAP immunoreactivity in fish gut. Cell and tissue research 18 20512593
2024 Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI. Alzheimer's & dementia : the journal of the Alzheimer's Association 17 38805359
2020 Discriminative value of glial fibrillar acidic protein (GFAP) as a diagnostic tool in acute stroke. Individual patient data meta-analysis. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 17 32907910