Alexander Disease
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What is Alexander disease?
Alexander disease is a rare disorder of the nervous system. It is considered one of the leukodystrophies, a group of disorders in which the primary abnormality is the inability to maintain myelin. Myelin is a whitish substance that wraps around certain nerve cells and ensures the rapid transmission of nerve impulses. If myelin is not properly maintained, the transmission of nerve impulses is disrupted. As myelin deteriorates in leukodystrophies such as Alexander disease, nervous system functions are impaired.
Most cases of Alexander disease begin before age 2 years (the infantile form). Signs and symptoms of the infantile form typically include an enlarged brain and head (megalencephaly), seizures, stiffness in the arms and/or legs (spasticity), mental retardation, and delayed physical development. Less frequently, onset occurs later in childhood (the juvenile form) or adulthood. Common problems in juvenile and adult forms of Alexander disease include speech abnormalities, swallowing difficulties, and poor coordination (ataxia).
Alexander disease is also characterized by abnormal protein deposits known as Rosenthal fibers, which are found in specialized brain cells called astroglial cells. Astroglial cells support and nourish nerve cells in the brain and spinal cord.
How common is Alexander disease?
The prevalence of Alexander disease is unknown. About 500 cases have been reported since the disorder was first described in 1949.
What genes are related to Alexander disease?
Mutations in the GFAP gene cause Alexander disease.
The GFAP gene provides instructions for making a protein called glial fibrillary acidic protein. Several molecules of this protein bind together to form intermediate filaments. Intermediate filaments are important for the normal activities of astroglial cells. Mutations in the GFAP gene alter the structure of glial fibrillary acidic protein. The altered protein probably disturbs the formation of normal intermediate filaments. As a result, glial fibrillary acidic protein may accumulate as a component of Rosenthal fibers and interfere with the normal activities of astroglial cells. It is not well understood how impaired astroglial cells contribute to the abnormal formation or maintenance of myelin.
How do people inherit Alexander disease?
Alexander disease is considered an autosomal dominant disorder, which means one copy of the altered gene in each cell is sufficient to cause the disease. Almost all cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In some rare adult cases, a GFAP mutation may be passed to children of an affected parent.
Source: National Institutes of Health
Research reports on luciferase from University of Wisconsin provide new insights
2009 JUL 27 - (NewsRx.com) -- Fresh data on luciferase are presented in the report 'Dual transgenic reporter mice as a tool for monitoring expression of glial fibrillary acidic protein.' According to a study from the United States, "Glial fibrillary acidic protein (GFAP) is the major intermediate filament protein of astrocytes, and its expression changes dramatically during development and following injury. To facilitate study of the regulation of GFAP expression, we have generated dual transgenic mice expressing both firefly luciferase under the control of a 2.2 kb human GFAP promoter and Renilla luciferase under the control of a 0.5 kb human Glyceraldehyde 3 phosphate dehydrogenase (GAPDH) promoter for normalization of the GFAP signal." "The GFAP-fLuc was highly expressed in brain compared to other tissues, and was limited to astrocytes, whereas the GAPDH-RLuc was more widely expressed. Normalization of the GFAP signal to the GAPDH signal reduced the inter-individual variability compared to using the GFAP signal alone. The GFAP/GAPDH ratio correctly reflected the up-regulation of GFAP that occurs following retinal degeneration in FVB/N mice because of the rd mutation. Following kainic acid-induced seizures, changes in the GFAP/GAPDH ratio precede those in total GFAP protein," wrote W. Cho and colleagues, University of Wisconsin. The researchers concluded: "In knock-in mice expressing the R236H Alexander disease mutant, GFAP promoter activity is only transiently elevated and may not entirely account for the accumulation of GFAP protein that takes place." Cho and colleagues published the results of their research in the Journal of Neurochemistry (Dual transgenic reporter mice as a tool for monitoring expression of glial fibrillary acidic protein. Journal of Neurochemistry, 2009;110(1):343-51). For additional information, contact W. Cho, University of Wisconsin-Madison, Waisman Center and Dept. of Comparative Biosciences, Madison, Wisconsin 53705 USA.. The publisher of the Journal of Neurochemistry can be contacted at: Blackwell Publishing Inc., 350 Main St., Malden, MA 02148, USA. Keywords: United States, Madison, Dehydrogenase, Enzyme Research, Enzymology, Luciferase, Neurochemistry. This article was prepared by Proteomics Weekly editors from staff and other reports. Copyright 2009, Proteomics Weekly via NewsRx.com.
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