Background: Alexander disease is caused by dominantly acting mutations in glial fibrillary acidic protein (GFAP), the major intermediate filament of astrocytes in the central nervous system.
Main body: In addition to the sequence variants that represent the origin of disease, GFAP accumulation also takes place, together leading to a gain-of-function that has sometimes been referred to as "GFAP toxicity." Whether the nature of GFAP toxicity in patients, who have mixtures of both mutant and normal protein, is the same as that produced by simple GFAP excess, is not yet clear.
Conclusion: The implications of these questions for the design of effective treatments are discussed.
Keywords: Antisense oligonucleotides; Astrocyte; GFAP.