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

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

Journal

Cell reports methods
ISSN: 2667-2375
Titre abrégé: Cell Rep Methods
Pays: United States
ID NLM: 9918227360606676

Informations de publication

Date de publication:
09 Oct 2024
Historique:
received: 28 03 2024
revised: 17 06 2024
accepted: 20 09 2024
medline: 17 10 2024
pubmed: 17 10 2024
entrez: 16 10 2024
Statut: aheadofprint

Résumé

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.

Identifiants

DOI: 10.1016/j.crmeth.2024.100876 PMID: 39413778
pubmed: 39413778
pii: S2667-2375(24)00259-5
doi: 10.1016/j.crmeth.2024.100876
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

100876

Informations de copyright

Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests We, the authors, have a patent application related to this work.

Auteurs

Shuyi Liu (S)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Naixue Yang (N)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Yaping Yan (Y)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Shaobo Wang (S)

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.

Jialing Chen (J)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Yichao Wang (Y)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Xue Gan (X)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Jiawen Zhou (J)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Guoqing Xie (G)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Hong Wang (H)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Tianzhuang Huang (T)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China.

Weizhi Ji (W)

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: wji@lpbr.cn.

Zhengbo Wang (Z)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: wangzb@lpbr.cn.

Wei Si (W)

State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan 650500, China. Electronic address: siw@lpbr.cn.

Classifications MeSH