Ginkgolide A improves the pleiotropic function and reinforces the neuroprotective effects by mesenchymal stem cell-derived exosomes in 6-OHDA-induced cell model of Parkinson's disease

Parkinson's disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal ce...

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Published in:Aging (Albany, NY.) NY.), 2023-02, Vol.15 (5), p.1358-1370
Main Authors: Chen, William Shao-Tsu, Lin, Tzu-Ying, Kuo, Chia-Hua, Hsieh, Dennis Jine-Yuan, Kuo, Wei-Wen, Liao, Shih-Chieh, Kao, Hui-Chuan, Ju, Da-Tong, Lin, Yu-Jung, Huang, Chih-Yang
Format: Article
Language:English
Subjects:
alpha-Synuclein - metabolism
Dopamine - metabolism
Exosomes
Humans
Mesenchymal Stem Cells - metabolism
Neuroprotective Agents - metabolism
Neuroprotective Agents - pharmacology
Oxidopamine - toxicity
Parkinson Disease - drug therapy
Parkinson Disease - metabolism
Research Paper
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Summary:Parkinson's disease (PD) is a common disorder attributed to the loss of midbrain dopamine (mDA) neurons and reduced dopamine secretion. Currently, the treatment regimes for PD comprise deep brain stimulations, however, it attenuates the PD progression marginally and does not improve neuronal cell death. We investigated the function of Ginkgolide A (GA) to reinforce Wharton's Jelly-derived mesenchymal stem cells (WJMSCs) for treating the model of PD. GA enhanced the self-renewal, proliferation, and cell homing function of WJMSCs as assessed by MTT and transwell co-culture assay with a neuroblastoma cell line. GA pre-treated WJMSCs can restore 6-hydroxydopamine (6-OHDA)-induced cell death in a co-culture assay. Furthermore, exosomes isolated from GA pre-treated WJMSCs significantly rescued 6-OHDA-induced cell death as determined by MTT assay, flow cytometry, and TUNEL assay. Western blotting showed that apoptosis-related proteins were decreased following GA-WJMSCs exosomal treatment which further improved mitochondrial dysfunction. We further demonstrated that exosomes isolated from GA-WJMSCs could restore autophagy using immunofluorescence staining and immunoblotting assay. Finally, we used the alpha-synuclein recombinant protein and found that exosomes derived from GA-WJMSCs led to the reduced aggregation of alpha-synuclein compared to that in control. Our results suggested that GA could be a potential candidate for strengthening stem cell and exosome therapy for PD.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.204526