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GFAP in health and disease
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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“Considering the differential abundance of GFAP in AD and APOEch, and as GFAP influences astrocyte morphology [45, 91, 92, 93], we analyzed morphometric descriptors related to the scale, complexity, and shape of both the astrocytes themselves and their spatial domains.”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [92]
In the citing paper
“Vimentin and GFAP link astrocyte structure and gliovascular function [90, 92], and are associated with cytoplasmic proteins [92] participating in signal transduction pathways [44, 45, 106, 107].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [92]
In the citing paper
“GFAP immunolabeling clearly delineates cell morphology [92].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: APOE3 Christchurch homozygote glioprotection (2023) · cites this paper as [92]
In the citing paper
“Consistent with greater neuronal degeneration27, we found a significant rise in the number of GFAP+ cells in the VTA of 3-month-old Tg2576 mice, demonstrating an increase in reactive astrocytes in response to DAergic neuronal loss.”
From Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease (2017) · cites this paper as [27]
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Metadata
- Authors
- Middeldorp, J., & Hol, E. M.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- 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)
- 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
- 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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