and injury can cause glial cells to react in detrimental ways. Glial scarring is a consequence of several neurodegenerative conditions, as well as injury that severs neural material. The scar is formed by astrocytes interacting with fibrous tissue to re-establish the glial margins around the central injury core and is partially caused by up-regulation of GFAP. Another condition directly related to GFAP is Alexander disease, a rare genetic disorder. Its symptoms include mental and physical retardation, dementia, enlargement of the brain and head, spasticity (stiffness of arms and/or legs), and seizures. The cellular mechanism of the disease is the presence of cytoplasmic accumulations containing GFAP and heat shock proteins, known as Rosenthal fibers. Mutations in the coding region of GFAP have been shown to contribute to the accumulation of Rosenthal fibers. Some of these mutations have been proposed to be detrimental to cytoskeleton formation as well as an increase in caspase 3 activity, which would lead to increased apoptosis of cells with these mutations. GFAP therefore plays an important role in the pathogenesis of Alexander disease. Notably, the expression of some GFAP isoforms have been reported to decrease in response to acute infection or neurodegeneration. Additionally, reduction in GFAP expression has also been reported in Wernicke's encephalopathy. The HIV-1 viral envelope glycoprotein gp120 can directly inhibit the phosphorylation of GFAP and GFAP levels can be decreased in response to chronic infection with HIV-1, varicella zoster, and pseudorabies. Decreases in GFAP expression have been reported in Down's syndrome, schizophrenia, bipolar disorder and depression. The generally high abundance of GFAP in the CNS has led to a great interest in GFAP as a blood biomarker of acute injury to the brain and spinal cord in different types of disease mechanisms, such as traumatic brain injury and cerebrovascular disease. Elevated blood levels of GFAP are also found in neuroinflammatory diseases, such as multiple sclerosis and neuromyelitis optica, a disease targeting astrocytes. In a study of 22 child patients undergoing extracorporeal membrane oxygenation (ECMO), children with abnormally high levels of GFAP were 13 times more likely to die and 11 times more likely to suffer brain injury than children with normal GFAP levels. Interactions Glial fibrillary acidic protein has been shown to interact with MEN1 and PSEN1. Isoforms Although GFAP alpha is the only isoform which is able to assemble homomerically, GFAP has 8 different isoforms which label distinct subpopulations of astrocytes in the