An accelerated Parkinson's disease monkey model using AAV-α-synuclein plus poly(ADP-ribose).

IF 4.3 Q1 BIOCHEMICAL RESEARCH METHODS
Cell Reports Methods Pub Date : 2024-10-21 Epub Date: 2024-10-15 DOI:10.1016/j.crmeth.2024.100876
Shuyi Liu, Naixue Yang, Yaping Yan, Shaobo Wang, Jialing Chen, Yichao Wang, Xue Gan, Jiawen Zhou, Guoqing Xie, Hong Wang, Tianzhuang Huang, Weizhi Ji, Zhengbo Wang, Wei Si
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引用次数: 0

Abstract

The etiology of Parkinson's disease (PD) remains elusive, and the limited availability of suitable animal models hampers research on pathogenesis and drug development. We report the development of a cynomolgus monkey model of PD that combines adeno-associated virus (AAV)-mediated overexpression of α-synuclein into the substantia nigra with an injection of poly(ADP-ribose) (PAR) into the striatum. Our results show that pathological processes were accelerated, including dopaminergic neuron degeneration, Lewy body aggregation, and hallmarks of inflammation in microglia and astrocytes. Behavioral phenotypes, dopamine transporter imaging, and transcriptomic profiling further demonstrate consistencies between the model and patients with PD. This model can help to determine the mechanisms underlying PD impacted by α-synuclein and PAR and aid in the accelerated development of therapeutic strategies for PD.

使用 AAV-α-synuclein 加聚(ADP-核糖)的加速帕金森病猴模型。
帕金森病(Parkinson's disease,PD)的病因仍然难以捉摸,合适的动物模型有限,阻碍了发病机制研究和药物开发。我们报告了一种黑腹黑质α-突触核蛋白腺相关病毒(AAV)介导的过表达与向纹状体注射聚(ADP-核糖)(PAR)相结合的帕金森病猴模型的开发情况。我们的研究结果表明,病理过程加速,包括多巴胺能神经元变性、路易体聚集以及小胶质细胞和星形胶质细胞的炎症特征。行为表型、多巴胺转运体成像和转录组分析进一步证明了该模型与帕金森病患者之间的一致性。该模型有助于确定α-突触核蛋白和PAR影响帕金森病的机制,并有助于加速帕金森病治疗策略的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cell Reports Methods
Cell Reports Methods Chemistry (General), Biochemistry, Genetics and Molecular Biology (General), Immunology and Microbiology (General)
CiteScore
3.80
自引率
0.00%
发文量
0
审稿时长
111 days
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