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

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

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

Cell Rep Methods. 2024 Oct 9:100876. doi: 10.1016/j.crmeth.2024.100876. Online ahead of print.

Authors

Shuyi Liu¹, Naixue Yang¹, Yaping Yan¹, Shaobo Wang², Jialing Chen¹, Yichao Wang¹, Xue Gan¹, Jiawen Zhou¹, Guoqing Xie¹, Hong Wang¹, Tianzhuang Huang¹, Weizhi Ji³, Zhengbo Wang⁴, Wei Si⁵

Affiliations

¹ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.
² State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Department of Nuclear Medicine, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650032, China.
³ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China; Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan 650500, China. Electronic address: [email protected].
⁴ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: [email protected].
⁵ State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: [email protected].

PMID: 39413778
DOI: 10.1016/j.crmeth.2024.100876

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.

Keywords: CP: Neuroscience; Parkinson’s disease; microglia; non-human primate; poly(ADP-ribose); α-synuclein.