Glial fibrillary acidic protein (GFAP) is one of a group of proteins which form the building blocks of what are called intermediate filaments. Intermediate filaments are found in astroglial cells, which help to maintain the brain and spinal cord. Astroglial cells are thought to play an important part in the formation of myelin, which allows impulses to pass along nerves, and they help create the blood brain barrier that controls which substances move from the circulation into the brain. When the genes for glial fibrillary acidic protein are faulty, GFAP has an abnormal structure. This can cause what is known as Alexander disease, a rare condition in which brain tissue is gradually destroyed.
Inside astroglial cells in the central nervous system, a number of glial fibrillary acidic protein molecules join together to form each intermediate filament. Intermediate filament protein strands combine to create networks which form part of an astroglial cell's skeleton, allowing it to function properly and helping it to maintain its shape. Astroglial cells are thought to affect the cells surrounding nerves, enabling them to produce a type of fat called myelin, which forms an insulating coat.
When a genetic disorder causes mutations in the glial fibrillary acidic protein gene, this can result in the production of abnormal GFAP. It is thought that the faulty glial fibrillary acidic protein prevents the normal process of intermediate filament creation, and abnormal GFAP builds up in cells. In Alexander disease, collections of protein known as Rosenthal fibers appear in astroglial cells. Glial fibrillary acidic protein is thought to contribute to this fiber formation. The astroglial cells no longer function properly and myelin becomes abnormal.
In Alexander disease, loss of myelin means that nerve impulses are not transmitted properly. The condition may develop in infancy, childhood or adulthood. What is known as the infantile form is the most common, with symptoms and signs seen in the first two years of life. Brain and head enlargement, limb stiffness, seizures and intellectual impairment may occur. Juvenile and adult Alexander disease are associated with seizures, poor coordination and difficulties with speech and swallowing.
While most Alexander disease patients have a mutation in the glial fibrillary acidic protein gene, the disorder is not always inherited. Although the condition is fatal and there is no cure, the outlook for people with Alexander disease is quite variable. The infantile type of the disease is normally fatal within six years, but patients with other forms typically survive longer, occasionally for decades.
