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利用病毒载体创建帕金森病动物模型。

Use of viral vectors to create animal models for Parkinson's disease.

机构信息

Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.

出版信息

Neurobiol Dis. 2012 Nov;48(2):189-201. doi: 10.1016/j.nbd.2011.12.038. Epub 2011 Dec 29.

DOI:10.1016/j.nbd.2011.12.038
PMID:22227451
Abstract

Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While sporadic in the majority of cases, PD-linked dominant mutations in the α-synuclein and LRRK-2 genes, and recessive mutations in the parkin, DJ-1 and PINK-1 genes have been identified in PD families in recent years. In this review we describe viral animal models for PD, i.e. models that are based on PD-associated mutations, and have been generated by viral delivery of the respective disease genes to the substantia nigra of rodents and non-human primates. To date, viral PD models comprise α-synuclein and LRRK-2-based overexpression models, as well as models that mimic parkin loss of function by overexpression of the parkin substrates Pael-R, CDCrel-1, p38/JTV or synphilin-1. These viral models provide valuable insights into Parkinson disease mechanisms, help to identify therapeutic targets and may contribute to the development of therapeutic approaches.

摘要

帕金森病是一种神经退行性疾病,其特征是黑质中多巴胺能神经元的进行性丧失。虽然大多数病例为散发性,但近年来已在帕金森病家族中发现了与 α-突触核蛋白和 LRRK-2 基因相关的显性突变,以及与 parkin、DJ-1 和 PINK-1 基因相关的隐性突变。在这篇综述中,我们描述了帕金森病的病毒动物模型,即基于与帕金森病相关的突变,并通过将相关疾病基因病毒递送至啮齿动物和非人灵长类动物的黑质而产生的模型。迄今为止,病毒 PD 模型包括基于 α-突触核蛋白和 LRRK-2 的过表达模型,以及通过过表达 parkin 底物 Pael-R、CDCrel-1、p38/JTV 或 synphilin-1 模拟 parkin 功能丧失的模型。这些病毒模型为帕金森病机制提供了有价值的见解,有助于确定治疗靶点,并可能有助于开发治疗方法。

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Use of viral vectors to create animal models for Parkinson's disease.利用病毒载体创建帕金森病动物模型。
Neurobiol Dis. 2012 Nov;48(2):189-201. doi: 10.1016/j.nbd.2011.12.038. Epub 2011 Dec 29.
2
New Developments in Genetic rat models of Parkinson's Disease.帕金森病基因大鼠模型的新进展。
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From genes to proteins in mendelian Parkinson's disease: an overview.从孟德尔帕金森病的基因到蛋白质:概述。
Anat Rec (Hoboken). 2009 Dec;292(12):1893-901. doi: 10.1002/ar.20968.
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Impaired mitochondrial dynamics and function in the pathogenesis of Parkinson's disease.线粒体动力学和功能受损在帕金森病发病机制中的作用
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Parkinson's disease.帕金森病。
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Impact of recent genetic findings in Parkinson's disease.帕金森病近期遗传学研究结果的影响
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Parkin gene therapy for alpha-synucleinopathy: a rat model of Parkinson's disease.用于α-突触核蛋白病的帕金基因疗法:帕金森病大鼠模型
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Stereotaxic Intracranial Delivery of Chemicals, Proteins or Viral Vectors to Study Parkinson's Disease.立体定向颅内递药(化学物质、蛋白质或病毒载体)以研究帕金森病。
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Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.α-突触核蛋白和 Tau 蛋白的传播:相关机制的系统比较
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Misfolded Protein Linked Strategies Toward Biomarker Development for Neurodegenerative Diseases.错误折叠蛋白与神经退行性疾病生物标志物开发策略相关联。
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Best Practices for Generating and Using Alpha-Synuclein Pre-Formed Fibrils to Model Parkinson's Disease in Rodents.生成和使用α-突触核蛋白原纤维以在啮齿动物中模拟帕金森病的最佳实践。
J Parkinsons Dis. 2018;8(2):303-322. doi: 10.3233/JPD-171248.
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Chronic MPTP administration regimen in monkeys: a model of dopaminergic and non-dopaminergic cell loss in Parkinson's disease.慢性 MPTP 给药方案在猴子中的应用:帕金森病多巴胺能和非多巴胺能细胞丧失的模型。
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Astroglia as a cellular target for neuroprotection and treatment of neuro-psychiatric disorders.星形胶质细胞作为神经保护和神经精神疾病治疗的细胞靶点。
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