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.

中文翻译：

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完善GFAP对亚历山大病的毒性概念。

背景技术亚历山大病是由神经胶质纤维酸性蛋白（GFAP）中星形胶质细胞在中枢神经系统中的主要中间细丝的显性作用突变引起的。主体除了代表疾病起源的序列变体之外，还发生了GFAP积累，一起导致功能获得，有时被称为“ GFAP毒性”。突变和正常蛋白混合的患者中，GFAP毒性的性质是否与单纯GFAP过量所产生的毒性性质相同，目前尚不清楚。结论讨论了这些问题对设计有效治疗方法的意义。