Progress in developing transgenic monkey model for Huntington's disease.
Progress in developing transgenic monkey model for Huntington's disease.
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DOI：
10.1007/s00702-017-1803-y
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发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Chan AWS
中科院分区：
文献类型：
--
作者：
Snyder BR;Chan AWS
亨廷顿氏病（HD）是一种复杂的神经退行性疾病，目前尚无治愈方法。虽然通常可以给予治疗以缓解症状，但与HD相关的神经病理学无法停止或逆转。HD的特征在于纹状体和相关通路的变性，其导致运动和认知功能的损害以及精神障碍。尽管存在HD的细胞和啮齿动物模型，但在转基因HD非人灵长类动物（NHP;即恒河猴; HD猴）中的纵向研究显示其进展与人类患者高度相似。通过磁共振成像（MRI）检查的进行性脑萎缩和白色物质完整性变化与皮质纹状体功能和神经病理学相关的认知行为下降一致。HD猴也表现出更高的焦虑和易怒/侵略性，类似于人类HD患者，其他模型系统尚未复制。虽然比较模型方法对于推进我们对HD发病机制的理解至关重要，但HD猴可以为临床前研究和可翻译结局指标的长期评估提供独特的平台。本文综述了转基因HD猴模型的研究进展以及HD临床前研究的发展前景。
Huntington’s disease (HD) is a complex neurodegenerative disorder that has no cure. Although treatments can often be given to relieve symptoms, the neuropathology associated with HD cannot be stopped or reversed. HD is characterized by degeneration of the striatum and associated pathways that leads to impairment in motor and cognitive functions as well as psychiatric disturbances. Although cell and rodent models for HD exist, longitudinal study in a transgenic HD nonhuman primate (NHP; i.e. rhesus macaque; HD monkeys) shows high similarity in its progression with human patients. Progressive brain atrophy and changes in white matter integrity examined by magnetic resonance imaging (MRI) are coherent with the decline in cognitive behaviors related to corticostriatal functions and neuropathology. HD monkeys also express higher anxiety and irritability/aggression similar to human HD patients that other model systems have not yet replicated. While a comparative model approach is critical for advancing our understanding of HD pathogenesis, HD monkeys could provide a unique platform for preclinical studies and long-term assessment of translatable outcome measures. This review summarizes the progress in the development of the transgenic HD monkey model and the opportunities for advancing HD preclinical research.
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影响因子：
2.4
作者：
Chan AW;Xu Y;Jiang J;Rahim T;Zhao D;Kocerha J;Chi T;Moran S;Engelhardt H;Larkin K;Neumann A;Cheng H;Li C;Nelson K;Banta H;Zola SM;Villinger F;Yang J;Testa CM;Mao H;Zhang X;Bachevalier J
通讯作者：
Bachevalier J
影响因子：
5.3
作者：
Cepeda, Carlos;Galvan, Laurie;Levine, Michael S.
通讯作者：
Levine, Michael S.
影响因子：
25
作者：
Canales, JJ;Graybiel, AM
通讯作者：
Graybiel, AM
DOI：
10.1176/appi.neuropsych.14100265
发表时间：
2015-09-01
影响因子：
2.9
作者：
Dale, Maria;van Duijn, Erik
通讯作者：
van Duijn, Erik
影响因子：
16.2
作者：
Crook ZR;Housman D
通讯作者：
Housman D