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重新审视百草枯诱导的散发性帕金森病样模型。

Revisiting the Paraquat-Induced Sporadic Parkinson's Disease-Like Model.

机构信息

Centro de Envejecimiento y Regeneración (CARE UC), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

Centro de Excelencia en Biomedicina de Magallanes (CEBIMA), Universidad de Magallanes, Punta Arenas, Chile.

出版信息

Mol Neurobiol. 2019 Feb;56(2):1044-1055. doi: 10.1007/s12035-018-1148-z. Epub 2018 Jun 3.

Abstract

Parkinson's disease (PD) is a major neurodegenerative disorder that affects 1-2% of the total global population. Despite its high prevalence and publication of several studies focused on understanding its pathology, an effective treatment that stops and/or reverses the damage to dopaminergic neurons is unavailable. Similar to other neurodegenerative disorders, PD etiology may be linked to several factors, including genetic susceptibility and environmental elements. Regarding environmental factors, several neurotoxic pollutants, including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), have been identified. Moreover, some pesticides/herbicides, such as rotenone, paraquat (PQ), maneb (MB), and mancozeb (MZ), cause neurotoxicity and induce a PD-like pathology. Based on these findings, several in vitro and in vivo PD-like models have been developed to understand the pathophysiology of PD and evaluate different therapeutic strategies to fight dopaminergic neurodegeneration. 6-OHDA and MPTP are common models used in PD research, and pesticide-based approaches have become secondary models of study. However, some herbicides, such as PQ, are commonly used by farming laborers in developing countries. Thus, the present review summarizes the relevant scientific background regarding the use and effects of chronic exposure to PQ in the context of PD. Similarly, we discuss the relevance of PD-like models developed using this agrochemical compound.

摘要

帕金森病(PD)是一种主要的神经退行性疾病,影响全球总人口的 1-2%。尽管其患病率很高,并且有几项研究致力于了解其病理学,但仍缺乏能够阻止和/或逆转多巴胺能神经元损伤的有效治疗方法。与其他神经退行性疾病类似,PD 的病因可能与多种因素有关,包括遗传易感性和环境因素。关于环境因素,已经确定了几种神经毒性污染物,包括 6-羟多巴胺(6-OHDA)和 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)。此外,一些农药/除草剂,如鱼藤酮、百草枯(PQ)、代森锰(MB)和代森锌(MZ),会引起神经毒性并诱导类似 PD 的病理学。基于这些发现,已经开发了几种体外和体内类似 PD 的模型,以了解 PD 的病理生理学,并评估不同的治疗策略来对抗多巴胺能神经退行性变。6-OHDA 和 MPTP 是 PD 研究中常用的模型,基于农药的方法已成为次要的研究模型。然而,一些除草剂,如 PQ,在发展中国家常被农业工人使用。因此,本综述总结了关于慢性接触 PQ 在 PD 背景下的使用和影响的相关科学背景。同样,我们讨论了使用这种农用化学品化合物开发的类似 PD 模型的相关性。

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