三核苷酸重复 RNA 在神经疾病和退行性变中的作用。
Roles of trinucleotide-repeat RNA in neurological disease and degeneration.
机构信息
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.
出版信息
Trends Neurosci. 2010 Jun;33(6):292-8. doi: 10.1016/j.tins.2010.03.004. Epub 2010 Apr 14.
Abstract
A large number of human diseases are caused by expansion of repeat sequences - typically trinucleotide repeats - within the respective disease genes. The abnormally expanded sequence can lead to a variety of effects on the gene: sometimes the gene is silenced, but in many cases the expanded repeat sequences confer toxicity to the mRNA and, in the case of polyglutamine diseases, to the encoded protein. This article highlights mechanisms by which the mRNAs with abnormally expanded repeats can confer toxicity leading to neuronal dysfunction and loss. Greater understanding of these mechanisms will provide the foundation for therapeutic advances for this set of human disorders.
摘要
大量人类疾病是由相应疾病基因内重复序列（通常是三核苷酸重复序列）的扩展引起的。异常扩展的序列可能会对基因产生多种影响：有时基因被沉默，但在许多情况下，扩展的重复序列会使 mRNA 产生毒性，并且在多聚谷氨酰胺疾病的情况下，还会使编码的蛋白质产生毒性。本文重点介绍了异常扩展的重复 mRNA 如何产生毒性，从而导致神经元功能障碍和丧失的机制。对这些机制的深入了解将为这一组人类疾病的治疗进展提供基础。
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