Galloway Jocelyn N, Nelson David L
Baylor College of Medicine, Interdepartmental Program in Cell & Molecular Biology, One Baylor Plaza, Room 904E, Houston, TX 77030, USA, Tel.: +1 713 798 7898, Fax.: +1 713 798 1116.
Future Neurol. 2009 Nov 1;4(6):785. doi: 10.2217/fnl.09.44.
Fragile X premutation carriers are at risk for developing a late-onset, progressive neurodegenerative disorder termed fragile X-associated tremor/ataxia syndrome (FXTAS). A growing body of evidence suggests the characteristic excess CGG repeat containing FMR1 mRNA observed in premutation carriers is pathogenic and leads to clinical features of FXTAS. The current model suggests premutation mRNA transcripts can induce the formation of intranuclear inclusions by the sequestration of RNA-binding proteins and other proteins. The sequestered proteins are prevented from performing their normal functions, which is thought to lead to the neuropathology-observed FXTAS. This paper discusses the existing evidence that microsatellite expansions at the level of RNA play a role in the disease pathogenesis of FXTAS and some of the approaches that may uncover downstream effects of expanded riboCGG expression.
脆性X前突变携带者有患一种迟发性、进行性神经退行性疾病的风险，该疾病称为脆性X相关震颤/共济失调综合征（FXTAS）。越来越多的证据表明，在前突变携带者中观察到的含有特征性过量CGG重复序列的FMR1 mRNA具有致病性，并导致FXTAS的临床特征。目前的模型表明，前突变mRNA转录本可通过隔离RNA结合蛋白和其他蛋白质诱导核内包涵体的形成。被隔离的蛋白质无法执行其正常功能，这被认为会导致FXTAS的神经病理学表现。本文讨论了现有证据，即RNA水平的微卫星扩增在FXTAS的疾病发病机制中起作用，以及一些可能揭示扩展的核糖CGG表达下游效应的方法。
