Huntington's disease: can mice lead the way to treatment?
Huntington's disease: can mice lead the way to treatment?
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DOI：
10.1016/j.neuron.2010.12.035
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发表时间：
2011-02-10
期刊：
影响因子：
16.2
通讯作者：
Housman D
中科院分区：
文献类型：
--
作者：
Crook ZR;Housman D
亨廷顿病和HD患者的小鼠模型显示运动和行为功能障碍，例如协调和记忆的进行性丧失，并且具有相似的转录谱和纹状体神经元萎缩。小鼠和人类疾病之间的明显差异包括HD中几乎完全的纹状体变性和罕见的核内包涵体，以及表达全长突变亨廷顿蛋白的小鼠没有表现出HD特征性的寿命缩短的事实。虽然迄今为止没有在小鼠模型中测试的临床干预措施延迟了疾病进展，但小鼠模型为研究潜在的致病过程和开发新的有效疗法提供了宝贵的工具。在寻找HD的有效治疗方法时，必须考虑人类和小鼠之间的固有差异，但人类HD和小鼠模型之间的惊人相似性支持了以下观点：这些模型是支持潜在临床治疗的鉴定和测试的生物学相关系统。
Mouse models for Huntington’s Disease and HD patients demonstrate motor and behavioral dysfunctions, such as progressive loss of coordination and memory, and share similar transcriptional profiles and striatal neuron atrophy. Clear differences between the mouse and human diseases include almost complete striatal degeneration and rarity of intranuclear inclusions in HD, and the fact that mice expressing full length mutant huntingtin do not demonstrate a shortened lifespan characteristic of HD. While no clinical interventions tested in mouse models to date have delayed disease progression, the mouse models provide an invaluable tool for both investigating the underlying pathogenic processes and developing new effective therapies. Inherent differences between humans and mice must be considered in the search for efficacious treatments for HD, but the striking similarities between human HD and mouse models support the view that these models are a biologically relevant system to support the identification and testing of potential clinical therapies.