Glial Fibrillary Acidic Protein (GFAP): on the 45th Anniversary of Its Discovery

Glial fibrillary acidic protein (GFAP) is the main component of intermediate filaments of the cytoskeleton of astrocytes. Over more than four decades of fundamental and applied studies, GFAP achieved the status of the classical marker for astroglia. Our review deals with the analysis and systematization of the literature data describing the peculiarities of the structural organization of the molecules of this protein, its isoform composition, and changes in expression of the GFAP gene in the course of CNS ontogenesis; the hierarchical principle of the formation of glial intermediate filaments is also described. A great deal of information about key reactions of post-translational modifications of GFAP and their role in the functioning of the above-mentioned protein is conveyed. Based on the modern literature data, the limited proteolysis of GFAP is considered not only a stage of catabolic transformation of this protein but also a mechanism underlying regulation of the dynamic properties of the cytoskeleton in astroglial cells. It is believed that the main functions of GFAP are the maintenance of specific morphology of astrocytes, control of migration of these cells, and maintenance of the stability of their processes; however, more and more findings are indicative of the involvement of this protein in the processes of cellular signalling and modulation of neuron-to-glia interactions. GFAP as a component of intermediate filaments of the cytoskeleton plays a key role in the development of reactive astrocytosis, i.e., of a typical response of the CNS to injury. Overexpression of GFAP or suppression of its biosynthesis reflect modifications of the functional activity of astrocytes related to damage to the nerve tissue, metabolic abnormalities, and development of neurodegenerative states. Quantitative estimation of GFAP and of its breakdown products, as well as that of anti-GFAP autoantibodies in biological fluids, are at present used as significant criteria in the diagnostics of neurodegenerative pathologies. Non-canonical functions of GFAP, which it fulfills in non-astrocyte units, are indicative of functional polymorphism of this protein and need further investigations.