Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model
Defective autophagy is one of the cellular hallmarks of Parkinson’s disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a ph...
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MDPI AG
2023-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/12/18/2310 |
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| author | Ru-Huei Fu Syuan-Yu Hong Hui-Jye Chen |
| author_facet | Ru-Huei Fu Syuan-Yu Hong Hui-Jye Chen |
| author_sort | Ru-Huei Fu |
| collection | DOAJ |
| description | Defective autophagy is one of the cellular hallmarks of Parkinson’s disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of <i>Acanthopanax senticosus</i>. It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in <i>C. elegans,</i> degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome–lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting <i>SIRT1</i>. The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD. |
| first_indexed | 2024-03-10T22:56:36Z |
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| last_indexed | 2024-03-10T22:56:36Z |
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| spelling | doaj.art-c05f9e804a54401aa1cf4f88708ef68c2023-11-19T10:00:14ZengMDPI AGCells2073-44092023-09-011218231010.3390/cells12182310Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> ModelRu-Huei Fu0Syuan-Yu Hong1Hui-Jye Chen2Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanGraduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, TaiwanDefective autophagy is one of the cellular hallmarks of Parkinson’s disease (PD). Therefore, a therapeutic strategy could be a modest enhancement of autophagic activity in dopamine (DA) neurons to deal with the clearance of damaged mitochondria and abnormal protein aggregates. Syringin (SRG) is a phenolic glycoside derived from the root of <i>Acanthopanax senticosus</i>. It has antioxidant, anti-apoptotic, and anti-inflammatory properties. However, whether it has a preventive effect on PD remains unclear. The present study found that SRG reversed the increase in intracellular ROS-caused apoptosis in SH-SY5Y cells induced by neurotoxin 6-OHDA exposure. Likewise, in <i>C. elegans,</i> degeneration of DA neurons, DA-related food-sensitive behaviors, longevity, and accumulation of α-synuclein were also improved. Studies of neuroprotective mechanisms have shown that SRG can reverse the suppressed expression of SIRT1, Beclin-1, and other autophagy markers in 6-OHDA-exposed cells. Thus, these enhanced the formation of autophagic vacuoles and autophagy activity. This protective effect can be blocked by pretreatment with wortmannin (an autophagosome formation blocker) and bafilomycin A1 (an autophagosome–lysosome fusion blocker). In addition, 6-OHDA increases the acetylation of Beclin-1, leading to its inactivation. SRG can induce the expression of SIRT1 and promote the deacetylation of Beclin-1. Finally, we found that SRG reduced the 6-OHDA-induced expression of miR-34a targeting <i>SIRT1</i>. The overexpression of miR-34a mimic abolishes the neuroprotective ability of SRG. In conclusion, SRG induces autophagy via partially regulating the miR-34a/SIRT1/Beclin-1 axis to prevent 6-OHDA-induced apoptosis and α-synuclein accumulation. SRG has the opportunity to be established as a candidate agent for the prevention and cure of PD.https://www.mdpi.com/2073-4409/12/18/2310Parkinson’s diseasesyringinSH-SY5Y cells6-hydroxydopamine (6-OHDA)autophagyBeclin-1 |
| spellingShingle | Ru-Huei Fu Syuan-Yu Hong Hui-Jye Chen Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model Cells Parkinson’s disease syringin SH-SY5Y cells 6-hydroxydopamine (6-OHDA) autophagy Beclin-1 |
| title | Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model |
| title_full | Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model |
| title_fullStr | Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model |
| title_full_unstemmed | Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model |
| title_short | Syringin Prevents 6-Hydroxydopamine Neurotoxicity by Mediating the MiR-34a/SIRT1/Beclin-1 Pathway and Activating Autophagy in SH-SY5Y Cells and the <i>Caenorhabditis elegans</i> Model |
| title_sort | syringin prevents 6 hydroxydopamine neurotoxicity by mediating the mir 34a sirt1 beclin 1 pathway and activating autophagy in sh sy5y cells and the i caenorhabditis elegans i model |
| topic | Parkinson’s disease syringin SH-SY5Y cells 6-hydroxydopamine (6-OHDA) autophagy Beclin-1 |
| url | https://www.mdpi.com/2073-4409/12/18/2310 |
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