GFAP in health and disease

Middeldorp, J.; Hol, E.M.

doi:10.1016/j.pneurobio.2011.01.005

Cited by 1,080Skin and Cellular Biology ResearchNeuroinflammation and Neurodegeneration MechanismsConnexins and lens biology

GFAP in health and disease

Middeldorp, J., Hol, E.M.·2011·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2011.01.005

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Abstract

Glial fibrillary acidic protein (GFAP) is the main intermediate filament protein in mature astrocytes, but also an important component of the cytoskeleton in astrocytes during development. Major recent developments in astrocyte biology and the discovery of novel intermediate filament functions enticed the interest in the function of GFAP. The discovery of various GFAP splice variants gave an additional boost to explore this protein in more detail. The structural role of GFAP in astrocytes has been widely accepted for a long time, but over the years, GFAP has been shown to be involved in astrocyte functions, which are important during regeneration, synaptic plasticity and reactive gliosis. Moreover, different subpopulations of astrocytes have been identified, which are likely to have distinctive tasks in brain physiology and pathology, and which are not only classified by their spatial and temporal appearance, but also by their specific expression of intermediate filaments, including distinct GFAP isoforms. The presence of these isoforms enhances the complexity of the astrocyte cytoskeleton and is likely to underlie subtype specific functions. In this review we discuss the versatility of the GFAP cytoskeletal network from gene to function with a focus on astrocytes during human brain development, aging and disease.

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The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission
Popoli, M., Yan, Z., McEwen, B. S., & Sanacora, G. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3138 · Cited by 1,393 · see citing works
Diversity of astrocyte functions and phenotypes in neural circuits
Khakh, B. S., & Sofroniew, M. V. (2015) · Nature Neuroscience · doi:10.1038/nn.4043 · Cited by 1,239 · see citing works
Astrocyte barriers to neurotoxic inflammation
Sofroniew, M. V. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3898 · Cited by 1,202 · see citing works
Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker
Yang, Z., & Wang, K. K. W. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.04.003 · Cited by 1,050 · see citing works
Glial fibrillary acidic protein (GFAP) and the astrocyte intermediate filament system in diseases of the central nervous system
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Blood GFAP as an emerging biomarker in brain and spinal cord disorders
Abdelhak, A., Foschi, M., Abu-Rumeileh, S., Yue, J. K., D’Anna, L., Huss, A., Oeckl, P., Ludolph, A. C., Kuhle, J., Petzold, A., et al. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00616-3 · Cited by 807 · see citing works
Astrocytes: a central element in neurological diseases
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Astrogliosis
Sofroniew, M. V. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a020420 · Cited by 695 · see citing works
Astrocyte Pathology in Major Depressive Disorder: Insights from Human Postmortem Brain Tissue
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Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy
Fang, B., McKeon, A. B., Hinson, S. R., Kryzer, T. J., Pittock, S. J., Aksamit, A. J., & Lennon, V. A. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2549 · Cited by 566 · see citing works
Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients
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The Indispensable Roles of Microglia and Astrocytes during Brain Development
Reemst, K., Noctor, S. C., Lucassen, P. J., & Hol, E. M. (2016) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2016.00566 · Cited by 516 · see citing works
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Current knowledge and pharmacological profile of berberine: An update
Kumar, A., Ekavali, Chopra, K., Mukherjee, M., Pottabathini, R., & Dhull, D. K. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.05.068 · Cited by 533 · see citing works
Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease
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Plasma glial fibrillary acidic protein is elevated in cognitively normal older adults at risk of Alzheimer’s disease
Chatterjee, P., Pedrini, S., Stoops, E., Goozee, K., Villemagne, V. L., Asih, P. R., Verberk, I. M. W., Dave, P., Taddei, K., Sohrabi, H. R., et al. (2021) · Translational Psychiatry · doi:10.1038/s41398-020-01137-1 · Cited by 439 · see citing works
Live imaging of astrocyte responses to acute injury reveals selective juxtavascular proliferation
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Age-associated Physiological and Pathological Changes at the Blood-Brain Barrier: A Review
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Astrocyte Heterogeneity: Impact to Brain Aging and Disease
Matias, I., Morgado, J., & Gomes, F. C. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00059 · Cited by 387 · see citing works
Lipid peroxidation and neurodegenerative disease
Reed, T. T. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.027 · Cited by 380 · see citing works
Hematogenous dissemination of glioblastoma multiforme
Müller, C., Holtschmidt, J., Auer, M., Heitzer, E., Lamszus, K., Schulte, A., Matschke, J., Langer-Freitag, S., Gasch, C., Stoupiec, M., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009095 · Cited by 329 · see citing works
Beyond the GFAP-Astrocyte Protein Markers in the Brain
Jurga, A. M., Paleczna, M., Kadluczka, J., & Kuter, K. Z. (2021) · Biomolecules · doi:10.3390/biom11091361 · Cited by 319 · see citing works
Astrocyte development: A Guide for the Perplexed
Molofsky, A. V., & Deneen, B. (2015) · Glia · doi:10.1002/glia.22836 · Cited by 311 · see citing works
GFAP Isoforms in Adult Mouse Brain with a Focus on Neurogenic Astrocytes and Reactive Astrogliosis in Mouse Models of Alzheimer Disease
Kamphuis, W., Mamber, C., Moeton, M., Kooijman, L., Sluijs, J. A., Jansen, A. H. P., Verveer, M., de Groot, L. R., Smith, V. D., Rangarajan, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042823 · Cited by 305 · see citing works
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Astrocytes in the initiation and progression of epilepsy
Vezzani, A., Ravizza, T., Bedner, P., Aronica, E., Steinhäuser, C., & Boison, D. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00727-5 · Cited by 272 · see citing works
Accumulation of amyloid-β by astrocytes result in enlarged endosomes and microvesicle-induced apoptosis of neurons
Söllvander, S., Nikitidou, E., Brolin, R., Söderberg, L., Sehlin, D., Lannfelt, L., & Erlandsson, A. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0098-z · Cited by 267 · see citing works
Human adult neurogenesis across the ages: An immunohistochemical study
Dennis, C. V., Suh, L. S., Rodriguez, M. L., Kril, J. J., & Sutherland, G. T. (2016) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12337 · Cited by 265 · see citing works
Cancer Stem Cell Hierarchy in Glioblastoma Multiforme
Bradshaw, A., Wickremsekera, A., Tan, S. T., Peng, L., Davis, P. F., & Itinteang, T. (2016) · Frontiers in Surgery · doi:10.3389/fsurg.2016.00021 · Cited by 255 · see citing works
Blood–Brain Barrier Breakdown: An Emerging Biomarker of Cognitive Impairment in Normal Aging and Dementia
Hussain, B., Fang, C., & Chang, J. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.688090 · Cited by 251 · see citing works
The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus
Cerbai, F., Lana, D., Nosi, D., Petkova-Kirova, P., Zecchi, S., Brothers, H. M., Wenk, G. L., & Giovannini, M. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045250 · Cited by 251 · see citing works
Biomarkers for Severity of Neonatal Hypoxic-Ischemic Encephalopathy and Outcomes in Newborns Receiving Hypothermia Therapy
Chalak, L. F., Sánchez, P. J., ADAMS-HUET, B. A., Laptook, A. R., Heyne, R. J., & Rosenfeld, C. R. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.10.067 · Cited by 247 · see citing works
Autoimmune glial fibrillary acidic protein astrocytopathy
Kunchok, A. C., Ζεκερίδου, Α., & McKeon, A. B. (2019) · Current Opinion in Neurology · doi:10.1097/wco.0000000000000676 · Cited by 245 · see citing works
Extensive uptake of α-synuclein oligomers in astrocytes results in sustained intracellular deposits and mitochondrial damage
Lindström, V., Gustafsson, G., Sanders, L. H., Howlett, E. H., Sigvardson, J., Kasrayan, A., Ingelsson, M., Bergström, J., & Erlandsson, A. (2017) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2017.04.009 · Cited by 233 · see citing works
Glial fibrillary acidic protein isoform expression in plaque related astrogliosis in Alzheimer's disease
Kamphuis, W., Middeldorp, J., Kooijman, L., Sluijs, J. A., Kooi, E., Moeton, M., Freriks, M., Mizee, M. R., & Hol, E. M. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.09.035 · Cited by 244 · see citing works
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Astrocytes have the capacity to act as antigen-presenting cells in the Parkinson’s disease brain
Rostami, J., Fotaki, G., Sirois, J., Mzezewa, R., Bergström, J., Essand, M., Healy, L., & Erlandsson, A. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01776-7 · Cited by 212 · see citing works
IOP induces upregulation of GFAP and MHC-II and microglia reactivity in mice retina contralateral to experimental glaucoma
Gallego, B. I., Salazar, J. J., de Hoz, R., Rojas, B., Ramírez, A. I., Salinas-Navarro, M., Ortín-Martínez, A., Valiente-Soriano, F. J., Avilés-Trigueros, M., Villegas-Perez, M. P., et al. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-92 · Cited by 224 · see citing works
Mesenchymal stem cell-derived extracellular vesicles ameliorate Alzheimer's disease-like phenotypes in a preclinical mouse model
Cone, A. S., Yuan, X., Sun, L. J., Duke, L. C., Vreones, M. P., Carrier, A. N., Kenyon, S. M., Carver, S. R., Cushing, S. D., Stimmell, A. C., et al. (2021) · Theranostics · doi:10.7150/thno.62069 · Cited by 224 · see citing works
Structural Remodeling of Astrocytes in the Injured CNS
Sun, D., & Jakobs, T. (2011) · The Neuroscientist · doi:10.1177/1073858411423441 · Cited by 219 · see citing works
Clinical and immunological characteristics of the spectrum of GFAP autoimmunity: a case series of 22 patients
Iorio, R., Damato, V., Evoli, A., Gessi, M., Gaudino, S., Lazzaro, V. D., Spagni, G., Sluijs, J. A., & Hol, E. M. (2017) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2017-316583 · Cited by 209 · see citing works
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EPIRETINAL PROLIFERATION SEEN IN ASSOCIATION WITH LAMELLAR MACULAR HOLES
Pang, C. E., Spaide, R. F., & Freund, K. B. (2014) · Retina · doi:10.1097/iae.0000000000000163 · Cited by 207 · see citing works
Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
Zhang, Z., Zoltewicz, J. S., Mondello, S., Newsom, K. J., Yang, Z., Yang, B., Kobeissy, F., Guingab, J., Glushakova, O., Robicsek, S., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092698 · Cited by 200 · see citing works
Age-Associated Changes in the Immune System and Blood–Brain Barrier Functions
Erickson, M. A., & Banks, W. A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071632 · Cited by 192 · see citing works
Inflammation in Parkinson's Disease
Tüfekçi, K. U., Meuwissen, R. L. J., Genç, Ş., & Genç, K. (2012) · Advances in protein chemistry and structural biology · doi:10.1016/b978-0-12-398314-5.00004-0 · Cited by 199 · see citing works
Control of autoimmune CNS inflammation by astrocytes
Rothhammer, V., & Quintana, F. J. (2015) · Seminars in Immunopathology · doi:10.1007/s00281-015-0515-3 · Cited by 214 · see citing works
Enteric <scp>GFAP</scp> expression and phosphorylation in Parkinson's disease
Clairembault, T., Kamphuis, W., Leclair‐Visonneau, L., Rolli‐Derkinderen, M., Coron, E., Neunlist, M., Hol, E. M., & Derkinderen, P. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12742 · Cited by 191 · see citing works
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Phenotypic Heterogeneity and Plasticity of Isocortical and Hippocampal Astrocytes in the Human Brain
Sosunov, A. A., Wu, X., Tsankova, N. M., Guilfoyle, E., McKhann, G. M., & Goldman, J. E. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4037-13.2014 · Cited by 185 · see citing works
Aberrant Calcium Signals in Reactive Astrocytes: A Key Process in Neurological Disorders
Shigetomi, E., Saito, K., Sano, F., & Koizumi, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20040996 · Cited by 171 · see citing works
Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease: Current Evidence and Future Perspectives
McGrowder, D. A., Miller, F. G., Vaz, K., Nwokocha, C. R., Wilson-Clarke, C. F., Anderson, M., Brown, J., Anderson-Jackson, L., Williams, L., Latore, L., et al. (2021) · Brain Sciences · doi:10.3390/brainsci11020215 · Cited by 167 · see citing works
Astrocytes are central in the pathomechanisms of vanishing white matter
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Authors: Middeldorp, J., & Hol, E. M.
Affiliations: Netherlands Institute for Neuroscience (NL)
Corresponding author: Hol, E.M.
ORCID: Middeldorp, J.
Hol, E.M.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2011-03
Volume: 93
Issue: 3
Pages: 421-443
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2011.01.005
OpenAlex: W1996241541
Cited by: 1,080
References: 251
Citations by year: 2026: 47 · 2025: 76 · 2024: 87 · 2023: 98 · 2022: 106 · 2021: 90 · 2020: 60 · 2019: 68 · 2018: 50 · 2017: 58 · 2016: 71 · 2015: 83 · 2014: 75 · 2013: 60 · 2012: 38
FWCI: 28.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
Keywords: glial fibrillary acidic protein, astrocytes, intermediate filaments, reactive gliosis, synaptic plasticity, brain regeneration, astrocyte subpopulations, brain development, brain aging, neurodegenerative diseases
MeSH terms: Aging, Amino Acid Sequence, Animals, Astrocytes, Brain, Cytoskeleton, Glial Fibrillary Acidic Protein, Humans, Molecular Sequence Data, Neurons, Sequence Alignment, Neurodegenerative Diseases, Protein Isoforms

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