RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model
RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model
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DOI：
10.1073/pnas.0501507102
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发表时间：
2005-04-19
影响因子：
11.1
通讯作者：
Davidson, BL
中科院分区：
文献类型：
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作者：
Harper, SQ;Staber, PD;Davidson, BL
亨廷顿病(HD)是一种致命的显性神经遗传病。HD是由HD外显子1上的多个谷氨酰胺重复序列(CAG密码子，Q)扩展引起的，使亨廷顿蛋白(HTT)获得了有毒的功能。目前，还没有针对HID的预防性治疗。RNA干扰(RNAi)通过直接降低疾病基因表达，成为治疗显性疾病的一种潜在的治疗工具。在这里，我们发现针对突变的人HTT的RNAi降低了细胞培养和HD小鼠脑中HTT的mRNA和蛋白的表达。重要的是，HTT基因沉默改善了与HID相关的行为和神经病理异常。我们的数据为RNAi在HD治疗中的进一步发展提供了支持。
Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HID. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HID. Our data provide support for the further development of RNAi for HD therapy.