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
{"title":"An accelerated Parkinson's disease monkey model using AAV-α-synuclein plus poly(ADP-ribose).","authors":"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","doi":"10.1016/j.crmeth.2024.100876","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":29773,"journal":{"name":"Cell Reports Methods","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Methods","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1016/j.crmeth.2024.100876","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/10/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
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.