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 a-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 a-synuclein and PAR and aid in the accelerated development of therapeutic strategies for PD.
基金:
National Key Research and Development Program of China [2018YFA0801400]; Natural Science Foundation of Yunnan Province [202202AG050018, 202102AA100053, 202401AS070086]; Natural Science Foundation of China [31960120]; Science and Tech-nology Plan of the Science and Technology Agency of Yunnan Province [202105AC160041]
第一作者机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China[3]Yunnan Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China
推荐引用方式(GB/T 7714):
Liu Shuyi,Yang Naixue,Yan Yaping,et al.Report An accelerated Parkinson's disease monkey model using AAV-a-synuclein plus poly(ADP-ribose)[J].CELL REPORTS METHODS.2024,4(10):doi:10.1016/j.crmeth.2024.100876.
APA:
Liu, Shuyi,Yang, Naixue,Yan, Yaping,Wang, Shaobo,Chen, Jialing...&Si, Wei.(2024).Report An accelerated Parkinson's disease monkey model using AAV-a-synuclein plus poly(ADP-ribose).CELL REPORTS METHODS,4,(10)
MLA:
Liu, Shuyi,et al."Report An accelerated Parkinson's disease monkey model using AAV-a-synuclein plus poly(ADP-ribose)".CELL REPORTS METHODS 4..10(2024)