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利用非人类灵长类动物模型来理解帕金森病中的相关过程。

The use of nonhuman primate models to understand processes in Parkinson's disease.

机构信息

HM CINAC, Hospital Universitario HM Puerta del Sur, Av. Carlos V, 70, Móstoles, 28938, Madrid, Spain.

Biomedical Research Center of Neurodegenerative Diseases (CIBERNED), Madrid, Spain.

出版信息

J Neural Transm (Vienna). 2018 Mar;125(3):325-335. doi: 10.1007/s00702-017-1715-x. Epub 2017 Mar 29.

Abstract

Research with animal models has led to critical health advances that have saved or improved the lives of millions of human beings. Specifically, nonhuman primate's genetic and anatomo-physiological similarities to humans are especially important for understanding processes like Parkinson's disease, which only occur in humans. Unambiguously, the unique contribution made by nonhuman primate research to our understanding of Parkinson's disease is widely recognized. For example, monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) parkinsonisms are responsive to dopamine replacement therapies, mimicking what is seen in PD patients. Moreover, groundbreaking neuroanatomical and electrophysiological studies using this monkey model in the 1980s and 1990s enabled researchers to identify the neuronal circuits responsible for the cardinal motor features of PD. This led to the development of subthalamic surgical ablation and deep brain stimulation, the current therapeutic gold standard for neurosurgical treatment. More recently, the mechanisms of α-synuclein spreading testing the prion hypothesis for PD have yielded exciting results. In this review, we discuss and highlight how the findings from nonhuman primate research contribute to our understanding of idiopathic Parkinson's disease.

摘要

动物模型研究带来了重大的健康进展,为数百万人类的生命拯救或改善做出了贡献。具体来说,非人类灵长类动物的遗传和解剖生理学与人类的相似性对于理解帕金森病等仅在人类中发生的过程尤为重要。毫无疑问,非人类灵长类动物研究对我们理解帕金森病的独特贡献得到了广泛认可。例如,具有 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)帕金森病的猴子对多巴胺替代疗法有反应,类似于 PD 患者的情况。此外,在 20 世纪 80 年代和 90 年代,使用这种猴子模型进行的开创性神经解剖学和电生理学研究使研究人员能够确定负责 PD 主要运动特征的神经元回路。这导致了苍白球切开术和深部脑刺激的发展,这是目前神经外科治疗的金标准。最近,α-突触核蛋白传播的机制测试了 PD 的朊病毒假说,取得了令人兴奋的结果。在这篇综述中,我们讨论并强调了非人类灵长类动物研究的发现如何有助于我们理解特发性帕金森病。

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