Animal Models of Parkinson's Disease.

IF 10.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Valina L Dawson, Ted M Dawson
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引用次数: 0

Abstract

Parkinson's disease (PD) is a complex genetic disorder that is associated with environmental risk factors and aging. Vertebrate genetic models, especially in mice, has aided the study of autosomal-dominant and autosomal-recessive PD. Mice are capable of exhibiting a broad range of phenotypes and coupled with their conserved genetic and anatomical structures provides unparalleled molecular and pathological tool to model human disease. These models used in combination with aging and PD-associated toxins have expanded our understanding of PD pathogenesis. Attempts to refine PD animal models using conditional approaches have yielded in vivo nigrostriatal degeneration that is instructive in ordering pathogenic signaling and in developing therapeutic strategies to cure or halt the disease. α-Synuclein preformed fibril (PFF) injections, which induce the aggregation of endogenous α-synuclein, remarkably recapitulate pathological processes observed in human PD. Here, we provide an overview of the generation and characterization of transgenic and knockout mice and the α-synuclein PFF models used to study PD followed by molecular insights that have been gleamed these PD mouse models.

帕金森病的动物模型。
帕金森病(PD)是一种复杂的遗传疾病,与环境危险因素和衰老有关。脊椎动物遗传模型,特别是小鼠,有助于常染色体显性和常染色体隐性PD的研究。小鼠能够表现出广泛的表型,加上它们保守的遗传和解剖结构,为模拟人类疾病提供了无与伦比的分子和病理工具。这些结合衰老和PD相关毒素的模型扩展了我们对PD发病机制的理解。使用条件方法改进PD动物模型的尝试已经产生了体内黑质纹状体变性,这对于排序致病信号和制定治疗策略来治愈或停止疾病具有指导意义。α-突触核蛋白预形成纤维(PFF)注射剂可诱导内源性α-突触核蛋白聚集,明显再现了PD的病理过程。在这里,我们概述了转基因和敲除小鼠的产生和表征,以及用于研究PD的α-突触核蛋白PFF模型,以及这些PD小鼠模型的分子见解。
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来源期刊
Cold Spring Harbor perspectives in medicine
Cold Spring Harbor perspectives in medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
14.30
自引率
1.90%
发文量
44
审稿时长
4-8 weeks
期刊介绍: Cold Spring Harbor Perspectives in Medicine is a monthly online publication comprising reviews on different aspects of a variety of diseases, covering everything from the molecular and cellular bases of disease to translational medicine and new therapeutic strategies. Cold Spring Harbor Perspectives in Medicine is thus unmatched in its depth of coverage and represents an essential source where readers can find informed surveys and critical discussion of advances in molecular medicine.
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