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Animal models of α-synucleinopathy for Parkinson disease drug development
Nature Reviews Neuroscience ( IF 34.7 ) Pub Date : 2017-07-13 00:00:00 , DOI: 10.1038/nrn.2017.75
James B. Koprich , Lorraine V. Kalia , Jonathan M. Brotchie

A major challenge in Parkinson disease (PD) will be to turn an emerging and expanding pipeline of novel disease-modifying candidate compounds into therapeutics. Novel targets need in vivo validation, and candidate therapeutics require appropriate preclinical platforms on which to define potential efficacy and target engagement before advancement to clinical development. We propose that α-synuclein (α-syn)-based mammalian models will be crucial for this process. Here, we review α-syn transgenic mouse models, viral vector models of α-syn overexpression and models of 'prion-like' spread of α-syn, and describe how each of these model types may contribute to PD drug discovery. We conclude by presenting our opinion on how to use a combination of these models through the late-stage preclinical, proof-of-principle investigation of novel therapeutics.

中文翻译:

帕金森病药物开发的α-突触核蛋白病变的动物模型

帕金森氏病(PD)的主要挑战是将新兴的疾病改良候选化合物转化为治疗药,并将其发展壮大。新型靶标需要体内验证,候选疗法需要合适的临床前平台,以在临床开发之前定义潜在的疗效和靶标参与度。我们建议基于α-突触核蛋白(α- syn)的哺乳动物模型对于这一过程至关重要。在这里,我们回顾α -syn转基因小鼠模型中,病毒载体机型α -syn表达和模型的朊病毒样'的蔓延α-syn,并描述每种模型类型如何有助于PD药物发现。我们通过对新型疗法的后期临床前,原则验证研究提出有关如何使用这些模型的组合的意见作为结论。
更新日期:2017-08-21
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