Fragile X-associated tremor/ataxia syndrome (FXTAS): pathology and mechanisms.
Fragile X-associated tremor/ataxia syndrome (FXTAS): pathology and mechanisms.
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DOI：
10.1007/s00401-013-1138-1
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发表时间：
2013-07
影响因子：
12.7
通讯作者：
Hagerman P
中科院分区：
文献类型：
--
作者：
Hagerman P
自2001年发现以来，我们对脆性X相关震颤/共济失调综合征（FXTAS）的理解经历了显着的转变。最初，FXTAS的特征仅限于成人发作的运动障碍，其定义正在扩大;此外，该疾病现在被认为是携带FMR 1基因前突变等位基因的儿童和成人中更广泛的临床多效性的一个方面。此外，FXTAS的核内包涵体，曾经被认为是CNS特异性标志物的疾病，现在已知广泛分布在多个非CNS组织中;这一观察结果从根本上改变了我们对疾病的概念，并可能为理解与前突变相关的各种医学问题提供基础。最近关于FXTAS潜在致病机制的研究表明，迟发性神经退行性疾病的起源实际上在于早期发育，这增加了前突变携带者之间所有形式的临床参与具有共同的潜在机制基础的可能性。我们对FXTAS发病机制中的触发事件的理解也有了很大进展，现在认为这涉及与microRNA生物发生有关的一种或多种核蛋白的螯合。此外，越来越多的证据表明，线粒体失调导致细胞功能下降和活力丧失，即使在新生儿时期，小鼠也是如此。总之，这些最新的发现为FXTAS的早期干预提供了希望，在明显疾病发作之前，以及治疗前突变携带者中其他形式的临床参与。
Since its discovery in 2001, our understanding of fragile X-associated tremor/ataxia syndrome (FXTAS) has undergone a remarkable transformation. Initially characterized rather narrowly as an adult-onset movement disorder, the definition of FXTAS is broadening; moreover, the disorder is now recognized as only one facet of a much broader clinical pleiotropy among children and adults who carry premutation alleles of the FMR1 gene. Furthermore, the intranuclear inclusions of FXTAS, once thought to be a CNS-specific marker of the disorder, are now known to be widely distributed in multiple non-CNS tissues; this observation fundamentally changes our concept of the disease, and may provide the basis for understanding the diverse medical problems associated with the premutation. Recent work on the pathogenic mechanisms underlying FXTAS indicates that the origins of the late-onset neurodegenerative disorder actually lie in early development, raising the likelihood that all forms of clinical involvement among premutation carriers have a common underlying mechanistic basis. There has also been great progress in our understanding of the triggering event(s) in FXTAS pathogenesis, which is now thought to involve sequestration of one or more nuclear proteins involved with microRNA biogenesis. Moreover, there is mounting evidence that mitochondrial dysregulation contributes to the decreased cell function and loss of viability, evident in mice even during the neonatal period. Taken together, these recent findings offer hope for early interventions for FXTAS, well before the onset of overt disease, and for the treatment of other forms of clinical involvement among premutation carriers.
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影响因子：
5.3
作者：
Chonchaiya W;Au J;Schneider A;Hessl D;Harris SW;Laird M;Mu Y;Tassone F;Nguyen DV;Hagerman RJ
通讯作者：
Hagerman RJ
影响因子：
16.2
作者：
Ash PE;Bieniek KF;Gendron TF;Caulfield T;Lin WL;Dejesus-Hernandez M;van Blitterswijk MM;Jansen-West K;Paul JW 3rd;Rademakers R;Boylan KB;Dickson DW;Petrucelli L
通讯作者：
Petrucelli L
DOI：
10.4088/jcp.08m04476
发表时间：
2009-06
期刊：
The Journal of clinical psychiatry
影响因子：
--
作者：
Bourgeois JA;Coffey SM;Rivera SM;Hessl D;Gane LW;Tassone F;Greco C;Finucane B;Nelson L;Berry-Kravis E;Grigsby J;Hagerman PJ;Hagerman RJ
通讯作者：
Hagerman RJ
DOI：
10.2310/jim.0b013e3181af59d6
发表时间：
2009-12
期刊：
Journal of investigative medicine : the official publication of the American Federation for Clinical Research
影响因子：
--
作者：
Berman RF;Willemsen R
通讯作者：
Willemsen R
影响因子：
5.6
作者：
Berman RF;Murray KD;Arque G;Hunsaker MR;Wenzel HJ
通讯作者：
Wenzel HJ