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帕金森病:模型系统目前带给我们的启示

Parkinson's disease: what the model systems have taught us so far.

作者信息

Ghatak Swagata, Trudler Dorit, Dolatabadi Nima, Ambasudhan Rajesh

机构信息

Neurodegenerative Disease Center, Scintillon Institute, San Diego, CA 92121, USA.

出版信息

J Genet. 2018 Jul;97(3):729-751.

Abstract

Parkinson's disease (PD) is a debilitating neurodegenerative disorder, for which people above the age of 60 show an increased risk. Although there has been great advancement in understanding the disease-related abnormalities in brain circuitry and development of symptomatic treatments, a cure for PD remains elusive. The discovery of PD associated gene mutations and environmental toxins have yielded animal models of the disease. These models could recapitulate several key aspects of PD, and provide more insights into the disease pathogenesis. They have also revealed novel aspects of the disease mechanism including noncell autonomous events and spreading of pathogenic protein species across the brain. Nevertheless, none of these models so far can comprehensively represent all aspects of the human disease. While the field is still searching for the perfect model system, recent developments in stem cell biology have provided a new dimension to modelling PD, especially doing it in a patient-specific manner. In the current review, we attempt to summarize the key findings in the areas discussed above, and highlight how the core PD pathology distinguishes itself from other neurodegenerative disorders while also resembling them in many aspects.

摘要

帕金森病(PD)是一种使人衰弱的神经退行性疾病,60岁以上人群患此病的风险会增加。尽管在理解与该疾病相关的脑回路异常以及开发对症治疗方法方面取得了巨大进展,但PD的治愈方法仍然难以捉摸。与PD相关的基因突变和环境毒素的发现产生了该疾病的动物模型。这些模型可以重现PD的几个关键方面,并为疾病发病机制提供更多见解。它们还揭示了疾病机制的新方面,包括非细胞自主事件和致病蛋白物种在大脑中的传播。然而,到目前为止,这些模型中没有一个能够全面代表人类疾病的所有方面。虽然该领域仍在寻找完美的模型系统,但干细胞生物学的最新进展为PD建模提供了一个新维度,特别是以患者特异性的方式进行建模。在当前的综述中,我们试图总结上述领域的关键发现,并强调核心PD病理学如何在与其他神经退行性疾病相似的许多方面又有别于它们。

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