Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker

• GFAP is tightly regulated at mRNA level and by PTMs.
• GFAP plays a critical role in astrogliosis after CNS injury and in neurodegeneration.
• GFAP is a potential drug target for Alexander's disease and neurodegeneration.
• GFAP and GFAP-BDPs are emerging biomarkers for TBI and neuroinjuries.

Glial fibrillary acidic protein (GFAP) is an intermediate filament (IF) III protein uniquely found in astrocytes in the central nervous system (CNS), non-myelinating Schwann cells in the peripheral nervous system (PNS), and enteric glial cells. GFAP mRNA expression is regulated by several nuclear-receptor hormones, growth factors, and lipopolysaccharides (LPSs). GFAP is also subject to numerous post-translational modifications (PTMs), while GFAP mutations result in protein deposits known as Rosenthal fibers in Alexander disease. GFAP gene activation and protein induction appear to play a critical role in astroglial cell activation (astrogliosis) following CNS injuries and neurodegeneration. Emerging evidence also suggests that, following traumatic brain and spinal cord injuries and stroke, GFAP and its breakdown products are rapidly released into biofluids, making them strong candidate biomarkers for such neurological disorders.