PUBLICATION
Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease
- Authors
- Wu, Y., Guo, Q., Gan, J., Duan, L., Zhao, H., Tai, H., Yang, C., Li, Y., Xu, Z., Yao, Y., Nie, Z., Yang, M., Li, S., Li, J., Su, B.
- ID
- ZDB-PUB-250327-12
- Date
- 2025
- Source
- Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica 58: e14282e14282 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Synucleins/genetics
- Synucleins/metabolism
- Dyneins/genetics
- Dyneins/metabolism
- Parkinson Disease*/genetics
- Parkinson Disease*/metabolism
- alpha-Synuclein/genetics
- alpha-Synuclein/metabolism
- Zebrafish*
- Autophagy*/genetics
- Autophagy*/physiology
- Axonal Transport/physiology
- Animals
- Disease Models, Animal*
- Dynactin Complex*/genetics
- Dynactin Complex*/metabolism
- Humans
- Animals, Genetically Modified
- Gene Knockdown Techniques
- Dopaminergic Neurons*/metabolism
- Dopaminergic Neurons*/pathology
- PubMed
- 40136228 Full text @ Braz. J. Med. Biol. Res.
Citation
Wu, Y., Guo, Q., Gan, J., Duan, L., Zhao, H., Tai, H., Yang, C., Li, Y., Xu, Z., Yao, Y., Nie, Z., Yang, M., Li, S., Li, J., Su, B. (2025) Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica. 58:e14282e14282.
Abstract
Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage of Parkinson's disease (PD), with axonal degeneration preceding the loss of cell bodies. Our previous study indicated that the dysfunctional retrograde axonal transport could lead to the death of dopaminergic neurons resulting in PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as the main molecule involved in retrograde axonal transport, was not affected. This study aimed to verify the hypothesis that dynactin rather than dynein may be one of the key factors in the retrograde degeneration of dopaminergic neurons in the early stage of PD. Dynactin morpholino was used to inhibit the expression of dynactin in transgenic (Vmat2:GFP) zebrafish, resulting in a significant decrease of diencephalon dopamine neurons and synuclein aggregation in the basal plate region. In the dopaminergic SH-SY5Y cell line, dynactin-siRNA knockdown resulted in the expression of dynein shifting from dispersed distribution to concentration in synapses and cytoplasm near axons, and the fusion rate of dynein to dynactin was decreased, especially in axons, which blocked the retrograde axonal transport of α-synuclein and autophagy flow. Our results linked the knockdown of dynactin gene to the dysfunction of axonal microtubule transport system, suggesting that dynactin may be one of the key factors contributing to the retrograde degeneration of dopaminergic neurons in the early stage of PD.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping