Glial Fibrillary Acidic Protein: The Intermediate Filament Protein of Astrocytes

Abstract

It is now well established that glial fibrillary acidic protein (GFAP) is the principal 8- to 9-nm intermediate filament in mature astrocytes of the central nervous system (CNS). More than 30 years ago, the value of GFAP as a prototype antigen in nervous tissue identification and as a standard marker for fundamental and applied research at an interdisciplinary level was recognized. As a member of the cytoskeletal protein family, GFAP is thought to be important in modulating astrocyte motility and shape by providing structural stability to astrocytic processes. In the CNS of higher vertebrates, following injury, either as a result of trauma, disease, genetic disorders, or chemical insult, astrocytes become reactive and respond in a typical manner, termed astrogliosis. Astrogliosis is characterized by rapid synthesis of GFAP and is demonstrated by increase in protein content or by immunostaining with GFAP antibody. In addition to the major application GFAP antisera for routine use in astrocyte identification in the CNS, the molecular cloning of the mouse gene in 1985 and the subsequent discovery of the gfa-2 promoter have both opened a new and rich realm for GFAP studies. These include antisense, null mice, and numerous promoter studies. GFAP knockout mice studies have shown the important role of GFA cytoskeleton in the astrocyte. The genetic basis for the only disease due to GFAP mutation, Alexander disease, has been demonstrated and confirmed. While the structural function of GFAP has become more acceptable, the use of GFAP antibodies and promoters continue to be valuable in studying CNS injury, disease, and development.