Glial fibrillary acidic protein (GFAP) is a type III intermediate filament protein belonging to the intermediate filament protein family. The GFAP gene in humans encodes the GFAP protein. The gene is located on chromosome 17. Several CNS cell types that include ependymal cells and astrocytes express GFAP proteins during development. Other human cells, such as keratinocytes, Leydig cells, chondrocytes, and osteocytes, also express GFAP. GFAP, along with the other three non-epithelial cells belonging to the same protein family, regulates the functions and structure of the cytoskeleton. Although many studies use GFAP as a cell marker, we have still not completely understood its role in the body.
Studies suggest a GFAP protein can help maintain cell shape and astrocyte mechanical strength. Type III intermediate filament proteins comprise three domains, head, rod, and tail. The rod domain may differ in its DNA sequence, but its protein structure is highly conserved. GFAP can form both a homodimer and heterodimer and can polymerize other proteins in the type III group. GFAP comprises eight different isoforms that make up distinct astrocyte subpopulations in the human brain. Out of these isoforms, GFAP alpha is the only one that can assemble homomerically. Another isoform, GFAP delta, is one of the most researched GFAP isoforms. Studies have linked GFAP delta isoform with neural stem cells.
You can also use the other names like GFAP and ALXDRD when searching for ‘What is GFAP?’ or ‘What is Glial fibrillary acidic protein’?
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As astrocytes express GFAP, it regulates crucial CNS processes that include cellular communication and efficient functioning of the blood-brain barrier. Studies have shown that the GFAP gene adjusts its filament network and regulates mitosis in the cell. Studies of the GFAP biomarker in knockout mice induce white matter structure deterioration, abnormal myelination, and deterioration of the blood-brain barrier. On the other hand, in GFAP knockout mice, Purkinje cells were unable to show their original structure, and these mice perform inefficiently in conditioning experiments. In vitro studies that use antisense RNA show that astrocytes lacking GFAP protein are incapable of forming normal neuronal extensions. GFAP hence, plays a critical role in CNS injury repair, especially to form glial scars throughout the CNS.
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We perform MSD, Luminex, and ELISA assays for detecting GFAP biomarker in plasma, serum, and other biological fluids. Following is a Sandwich-based ELISA protocol used to detect GFAP protein in any biological fluids.
We begin the GFAP test with a microtiter plate, pre-coated with a GFAP-specific antibody. We then add 100 μl of standard or samples, followed by a GFAP specific biotin-conjugated antibody. Next, we incubate the wells with Avidin-conjugated HRP. We then add a TMB substrate solution in each well. The wells containing all three biotin-conjugated antibodies, GFAP, and enzyme-conjugated Avidin exhibit a change in color. Lastly, we end the reaction by adding a sulphuric acid solution and measure the color change spectrophotometrically at 450 nm (± 10 nm). We then compare the Optical Density (OD) with the standard curve and determine GFAP concentration.
The assay for GFAP immunoreactivity has a detection range of 31.2 pg/ml to 2000 pg/ml with a minimum detectable dose of < 10.2 pg/ml. The GFAP assay is highly specific, with an intra-assay precision of < 10% and inter-assay precision of <12%.
Studies have associated improper GFAP regulation with several disorders. GFAP dysregulation induces glial cells to cause detrimental injuries. Post-injury, the cells upregulate GFAP protein levels, and they interact with astrocytes and fibrous tissues to form a scar that re-establishes the glial margins. Alexander disease is another condition directly related to the presence of the GFAP. Alexander disease is a rare genetic disorder with symptoms including dementia, mental and physical retardation, seizures, and head and brain size enlargements.
To learn more about the biological role of GFAP and GFAP immunoreactivity, explore the resources below.
https://ghr.nlm.nih.gov/gene/GFAP
https://www.genecards.org/cgi-bin/carddisp.pl?gene=GFAP
https://www.uniprot.org/uniprot/P14136
https://www.omim.org/entry/137780
https://www.sciencedirect.com/topics/neuroscience/glial-fibrillary-acidic-protein
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