Glial fibrillary acidic protein (GFAP) is a key intermediate filament (IF) III protein responsible for maintaining the mechanical strength of glia cells by supporting their cytoskeleton structure. GFAP is expressed in astrocytes in the CNS, non-myelinating Schwann cells in the PNS, and enteric glial cells¹.

GFAP has a structural organization that is typical to class III IF proteins: it has a head, rod, and tail domains. The N-terminal head domain is important for filament formation and the C-terminal domain is important for oligomerization².

GFAP is encoded by a single gene mapped to human chromosome 17q21. To date, 10 isoforms/splice variants have been identified. GFAP is tightly regulated: both at mRNA transcription level and by phosphorylation and other post-translational modifications. A number of growth factors such as CNTF, FGF and TGF-β can induce GFAP gene transcription activation leading to increased GFAP protein levels³.

Single nucleotide polymorphism (SNP) in GFAP results in the formation of Rosenthal fibers that cause Alexander Disease, hence, GFAP is a potential drug target for the treatment of this disease. A number of GFAP mutations were found in the coding and in the promoter regions of Alexander disease patients⁴.

GFAP gene activation and protein induction appear to play a critical role in astroglia cell activation (astrogliosis) following CNS injuries and neurodegeneration. GFAP protein and its breakdown products are rapidly released into biofluids following traumatic brain and spinal cord injuries and stroke, making them strong candidate biomarkers for such neurological disorders⁵.