Myotonic dystrophies 1 and 2: complex diseases with complex mechanisms.
Myotonic dystrophies 1 and 2: complex diseases with complex mechanisms.
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DOI：
10.2174/138920210790886844
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发表时间：
2010-04
期刊：
影响因子：
2.6
通讯作者：
Timchenko L
中科院分区：
文献类型：
--
作者：
Schoser B;Timchenko L
两种多系统疾病，强直性肌营养不良1型和2型（DM 1和DM 2），是由含有重复CUG和CCUG元件的扩增的非编码RNA积累引起的复杂神经肌肉疾病。这些突变的相似性表明这两种疾病的机制相似。扩增的CUGn和CCUGn RNA主要靶向两种RNA结合蛋白MBNL 1和CUGBP 1，提高CUGBP 1的水平并降低MBNL 1的水平。这些改变改变了由这些蛋白质调节的RNA的加工。尽管已经证明了CUGn/CCUGn RNA对DM细胞中RNA稳态的总体毒性，但使这些RNA具有毒性的机制仍然不清楚。目前的观点是RNA CUGn和CCUGn的毒性仅与DM患者的整体错误剪接相关。然而，越来越多的新发现表明，CUGn和CCUGn RNA的扩增错误调节了DM 1和DM 2患者细胞核和细胞质中的几条额外途径。这篇综述的目的是讨论这两种疾病在临床表现和分子遗传学方面的异同。我们还将讨论由CUG和CCUG重复序列引起的DM 1和DM 2分子异常的复杂性，并总结CUG和CCUG重复序列毒性的结果。
Two multi-system disorders, Myotonic Dystrophies type 1 and type 2 (DM1 and DM2), are complex neuromuscular diseases caused by an accumulation of expanded, non-coding RNAs, containing repetitive CUG and CCUG elements. Similarities of these mutations suggest similar mechanisms for both diseases. The expanded CUGn and CCUGn RNAs mainly target two RNA binding proteins, MBNL1 and CUGBP1, elevating levels of CUGBP1 and reducing levels of MBNL1. These alterations change processing of RNAs that are regulated by these proteins. Whereas overall toxicity of CUGn/CCUGn RNAs on RNA homeostasis in DM cells has been proven, the mechanisms which make these RNAs toxic remain illusive. A current view is that the toxicity of RNA CUGn and CCUGn is associated exclusively with global mis-splicing in DM patients. However, a growing number of new findings show that the expansion of CUGn and CCUGn RNAs mis-regulates several additional pathways in nuclei and cytoplasm of cells from patients with DM1 and DM2. The purpose of this review is to discuss the similarities and differences in the clinical presentation and molecular genetics of both diseases. We will also discuss the complexity of the molecular abnormalities in DM1 and DM2 caused by CUG and CCUG repeats and will summarize the outcomes of the toxicity of CUG and CCUG repeats.
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影响因子：
3.5
作者：
Ho, TH;Bundman, D;Cooper, TA
通讯作者：
Cooper, TA
DOI：
10.1523/jneurosci.1983-09.2009
发表时间：
2009-07-15
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Huichalaf C;Schoser B;Schneider-Gold C;Jin B;Sarkar P;Timchenko L
通讯作者：
Timchenko L
影响因子：
64.8
作者：
BUXTON, J;SHELBOURNE, P;JOHNSON, K
通讯作者：
JOHNSON, K
影响因子：
7
作者：
Gerbasi, Vincent R.;Link, Andrew J.
通讯作者：
Link, Andrew J.
影响因子：
5.6
作者：
Chen, Wei;Wang, Yucheng;Li, Yi-Ping
通讯作者：
Li, Yi-Ping