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在体内鼠源α-突触核蛋白原纤维模型中观察到的表型概述。

A Summary of Phenotypes Observed in the In Vivo Rodent Alpha-Synuclein Preformed Fibril Model.

机构信息

The Michael J. Fox Foundation for Parkinson'sResearch, New York, NY, USA.

出版信息

J Parkinsons Dis. 2021;11(4):1555-1567. doi: 10.3233/JPD-212847.

Abstract

The use of wildtype recombinant alpha-synuclein preformed fibrils (aSyn PFFs) to induce endogenous alpha-synuclein to form pathological phosphorylation and trigger neurodegeneration is a popular model for studying Parkinson's disease (PD) biology and testing therapeutic strategies. The strengths of this model lie in its ability to recapitulate the phosphorylation/aggregation of aSyn and nigrostriatal degeneration seen in PD, as well as its suitability for studying the progressive nature of PD and the spread of aSyn pathology. Although the model is commonly used and has been adopted by many labs, variability in observed phenotypes exists. Here we provide summaries of the study design and reported phenotypes from published reports characterizing the aSyn PFF in vivo model in rodents following injection into the brain, gut, muscle, vein, peritoneum, and eye. These summaries are designed to facilitate an introduction to the use of aSyn PFFs to generate a rodent model of PD-highlighting phenotypes observed in papers that set out to thoroughly characterize the model. This information will hopefully improve the understanding of this model and clarify when the aSyn PFF model may be an appropriate choice for one's research.

摘要

使用野生型重组α-突触核蛋白原纤维(aSyn PFFs)诱导内源性α-突触核蛋白形成病理性磷酸化并引发神经退行性变,是研究帕金森病(PD)生物学和测试治疗策略的一种流行模型。该模型的优势在于能够重现 PD 中观察到的αSyn 的磷酸化/聚集和黑质纹状体变性,以及适合研究 PD 的进行性和αSyn 病理学的传播。尽管该模型被广泛应用,并被许多实验室采用,但观察到的表型存在变异性。在这里,我们提供了已发表的研究设计和报告表型的摘要,这些研究设计和报告表型用于描述将 aSyn PFF 注射到大脑、肠道、肌肉、静脉、腹膜和眼睛后,在啮齿动物体内诱导 PD 的 aSyn PFF 模型。这些摘要旨在促进使用 aSyn PFF 来生成 PD 啮齿动物模型的介绍-突出那些旨在彻底描述该模型的论文中观察到的表型。希望这些信息将有助于更好地理解该模型,并阐明在何时选择 aSyn PFF 模型作为研究的合适选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c226/8609716/2c84a415ba69/jpd-11-jpd212847-g001.jpg

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