Premotor parkinsonism models.
Premotor parkinsonism models.
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DOI：
10.1016/s1353-8020(13)70007-5
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发表时间：
2014-01-01
影响因子：
4.1
通讯作者：
Fernagut, Pierre-Olivier
中科院分区：
文献类型：
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作者：
Bezard, Erwan;Fernagut, Pierre-Olivier
除了运动症状外，帕金森病还与许多早于运动症状出现的非运动症状有关。最常见和最具预测性的运动前症状包括嗅觉功能障碍、快速眼动睡眠行为障碍 (RBD) 和便秘。基于毒素或基因的模型的几项研究专门研究了运动前环境中的这些非运动体征。改变的嗅觉辨别力已在基于毒素和基于基因的模型中重现，并且遗传模型也可能重现潜在的病理生理机制。睡眠改变也已得到证实，主要是在基于毒素的模型中，并且 RBD 样特征可以在非人类灵长类动物中得到证实。胃肠道功能障碍和相关的肠道病理学在毒素和遗传模型中均得到再现，显示出结肠运动减少和肠道 α-突触核蛋白积累。这篇综述描述了在毒素模型和基因模型中重述的主要运动前症状、它们与人类疾病的相关性，以及它们了解早期症状和疾病进展的潜在机制的潜力。
Aside from motor symptoms, Parkinson's disease is associated with a number of non-motor symptoms arising many years before motor signs. The most prevalent and predictive premotor symptoms include olfactory dysfunction, REM sleep behaviour disorder (RBD) and constipation. Several studies in toxin- or gene-based models have specifically investigated these non-motor signs in a premotor context. Altered olfactory discrimination has been reproduced both in toxin- and in gene-based models, and genetic models may also reproduce the underlying pathophysiological mechanisms. Sleep alterations have also been demonstrated, mostly in toxin-based models, and RBD-like features can be demonstrated in non-human primates. Gastrointestinal dysfunction and associated enteric pathology are reproduced both in toxin and genetic models displaying reduced colonic motility and enteric alpha-synuclein accumulation. This review describes the main premotor symptoms that are recapitulated both in toxin- and in gene-based models, their relevance to the human disease, and their potential to understand the underlying mechanisms of early symptoms and disease progression.