Transgenic nonhuman primates for neurodegenerative diseases.
Transgenic nonhuman primates for neurodegenerative diseases.
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DOI：
10.1186/1477-7827-2-39
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发表时间：
2004-06-16
期刊：
影响因子：
--
通讯作者：
Chan, Anthony W S
中科院分区：
文献类型：
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作者：
Chan, Anthony W S
代表人类疾病的动物模型构成了理解疾病发病机制和开发有效疗法的重要工具。神经退行性疾病是涉及神经病理学和精神病学改变的复杂疾病。尽管已经建立了阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）的转基因和基因敲入小鼠模型，但是已经认识到在临床方面的有限代表性，并且啮齿动物模型缺乏真正的神经变性。已有非人灵长类动物（NHP）化学诱导HD和PD的报道，然而，内在遗传因素在疾病发展中的作用尚不确定。非人灵长类动物在遗传、神经解剖和认知/行为特征方面与人类非常相似。因此，神经退行性疾病的NHP模型的开发比使用其他动物物种的方法更有希望成功发现诊断，治疗和治愈。因此，携带与患者相似的突变基因的转基因NHP将有助于阐明我们对疾病发作和进展的理解。此外，通过高分辨率脑成像技术如MRI监测转基因NHP中的疾病发作和发展，以及行为和认知测试都可以在NHP中同时进行，但不能在其他动物模型中进行。此外，由于NHP和人类之间的运动库的相似性，还可以将NHP模型中观察到的神经综合征与患者中观察到的神经综合征进行比较。了解遗传缺陷与生理变化（如氧化损伤）之间的相关性将有助于更好地了解疾病进展以及为高危人群开发患者治疗、药物和预防方法。转基因NHP模型在理解遗传疾病在开发有效干预措施和药物方面的作用方面的影响是可以预见的。
Animal models that represent human diseases constitute an important tool in understanding the pathogenesis of the diseases, and in developing effective therapies. Neurodegenerative diseases are complex disorders involving neuropathologic and psychiatric alterations. Although transgenic and knock-in mouse models of Alzheimer's disease, (AD), Parkinson's disease (PD) and Huntington's disease (HD) have been created, limited representation in clinical aspects has been recognized and the rodent models lack true neurodegeneration. Chemical induction of HD and PD in nonhuman primates (NHP) has been reported, however, the role of intrinsic genetic factors in the development of the diseases is indeterminable. Nonhuman primates closely parallel humans with regard to genetic, neuroanatomic, and cognitive/behavioral characteristics. Accordingly, the development of NHP models for neurodegenerative diseases holds greater promise for success in the discovery of diagnoses, treatments, and cures than approaches using other animal species. Therefore, a transgenic NHP carrying a mutant gene similar to that of patients will help to clarify our understanding of disease onset and progression. Additionally, monitoring disease onset and development in the transgenic NHP by high resolution brain imaging technology such as MRI, and behavioral and cognitive testing can all be carried out simultaneously in the NHP but not in other animal models. Moreover, because of the similarity in motor repertoire between NHPs and humans, it will also be possible to compare the neurologic syndrome observed in the NHP model to that in patients. Understanding the correlation between genetic defects and physiologic changes (e.g. oxidative damage) will lead to a better understanding of disease progression and the development of patient treatments, medications and preventive approaches for high risk individuals. The impact of the transgenic NHP model in understanding the role which genetic disorders play in the development of efficacious interventions and medications is foreseeable.