An accelerated Parkinson’s disease monkey model using AAV-α-synuclein plus poly(ADP-ribose)
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.
Authors
- Jia‐wen Zhou (ORCID: https://orcid.org/0000-0002-6817-1071)
- Yaping Yan (ORCID: https://orcid.org/0000-0003-2434-0432)
- Shuyi Liu (ORCID: https://orcid.org/0000-0002-2065-156X)
- Wei Si
- Xue Gan (ORCID: https://orcid.org/0000-0002-8187-8426)
- Zhengbo Wang (ORCID: https://orcid.org/0000-0002-4717-5137)
- Weizhi Ji (ORCID: https://orcid.org/0000-0003-2550-4224)
- Hong Wang (ORCID: https://orcid.org/0000-0003-0165-3559)
- Tianzhuang Huang
- Nan Yang (ORCID: https://orcid.org/0000-0002-1549-3309)
- Shaobo Wang (ORCID: https://orcid.org/0000-0001-7775-6760)
- Jialing Chen (ORCID: https://orcid.org/0000-0001-5186-3488)
- Guoqing Xie (ORCID: https://orcid.org/0009-0002-0448-7402)
- Yichao Wang (ORCID: https://orcid.org/0009-0008-6627-350X)
Institutions
- Kunming University of Science and Technology (CN)
Publication Details
- Journal
- Cell Reports Methods
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.crmeth.2024.100876
- Citations
- 3
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.11
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Yunnan Province
- National Natural Science Foundation of China-Yunnan Joint Fund
- National Key Research and Development Program of China
- Cultivating Plan Program for the Leader in Science and Technology of Yunnan Province
- National Key Research and Development Program of China Stem Cell and Translational Research