Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models
Background: Salsolinol (SAL) is a dopamine metabolite and endogenous neurotoxin that exerts neurotoxicity to dopaminergic neurons and is involved in the genesis of Parkinson’s disease (PD). However, the machinery underlying SAL-induced neurotoxicity in PD is still being elucidated...
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IMR Press
2025-02-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL26679 |
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| author | Hongquan Wang Shuang Wu Qiang Li Huiyan Sun Yumin Wang |
| author_facet | Hongquan Wang Shuang Wu Qiang Li Huiyan Sun Yumin Wang |
| author_sort | Hongquan Wang |
| collection | DOAJ |
| description | Background: Salsolinol (SAL) is a dopamine metabolite and endogenous neurotoxin that exerts neurotoxicity to dopaminergic neurons and is involved in the genesis of Parkinson’s disease (PD). However, the machinery underlying SAL-induced neurotoxicity in PD is still being elucidated. Methods: In the present study, we first used RNA-seq and KEGG analysis to examine differentially expressed genes in SAL-challenged SH-SY5Y cells. PD animal models were established and treated with acteoside. Cell viability assays, lipid peroxidation assessments (malondialdehyde [MDA] and 4-Hydroxynonenal [4-HNE]), immunoblot, and transmission electron microscopy were used to confirm acteoside-mediated inhibition of ferroptosis and its neuroprotective effect on dopaminergic (DA) neurons. Results: We found that ferroptosis-related pathway was enriched by SAL. SAL inducing ferroptosis through upregulating long-chain acyl-CoA synthetase family member 4 (ACSL4) in SH-SY5Y cells, which neurotoxic effect was reversed by ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). Acteoside, a phenylethanoid glycoside of plant origin with a neuroprotective effect, attenuates SAL-induced neurotoxicity by inhibiting ferroptosis in in vitro and in vivo PD models through downregulating ACSL4. Conclusions: The present study revealed a novel molecular mechanism underlying SAL-induced neurotoxicity via induction of ferroptosis in PD, and uncovered a new pharmacological effect against PD through inhibiting ferroptosis. This study highlights SAL-induced neurotoxicity via ferroptosis as a potential therapeutic target in PD. |
| format | Article |
| id | doaj-art-de9eb8e67a734f2c923b2cf099c364b8 |
| institution | DOAJ |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-de9eb8e67a734f2c923b2cf099c364b82025-08-20T03:04:43ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-02-013022667910.31083/FBL26679S2768-6701(24)01584-3Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease ModelsHongquan Wang0Shuang Wu1Qiang Li2Huiyan Sun3Yumin Wang4Department of Geriatrics, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, 100049 Beijing, ChinaDepartment of Neurology, Zhongnan Hospital of Wuhan University, 430000 Wuhan, Hubei, ChinaDepartment of Neurology, The Affiliated Hospital of Chifeng University, 024005 Chifeng, Inner Mongolia, ChinaChifeng University Health Science Center, 024000 Chifeng, Inner Mongolia, ChinaDepartment of Respiratory and Critical Care Medicine, Aerospace Center Hospital, Peking University Aerospace School of Clinical Medicine, 100049 Beijing, ChinaBackground: Salsolinol (SAL) is a dopamine metabolite and endogenous neurotoxin that exerts neurotoxicity to dopaminergic neurons and is involved in the genesis of Parkinson’s disease (PD). However, the machinery underlying SAL-induced neurotoxicity in PD is still being elucidated. Methods: In the present study, we first used RNA-seq and KEGG analysis to examine differentially expressed genes in SAL-challenged SH-SY5Y cells. PD animal models were established and treated with acteoside. Cell viability assays, lipid peroxidation assessments (malondialdehyde [MDA] and 4-Hydroxynonenal [4-HNE]), immunoblot, and transmission electron microscopy were used to confirm acteoside-mediated inhibition of ferroptosis and its neuroprotective effect on dopaminergic (DA) neurons. Results: We found that ferroptosis-related pathway was enriched by SAL. SAL inducing ferroptosis through upregulating long-chain acyl-CoA synthetase family member 4 (ACSL4) in SH-SY5Y cells, which neurotoxic effect was reversed by ferroptosis inhibitors ferrostatin-1 (Fer-1) and deferoxamine (DFO). Acteoside, a phenylethanoid glycoside of plant origin with a neuroprotective effect, attenuates SAL-induced neurotoxicity by inhibiting ferroptosis in in vitro and in vivo PD models through downregulating ACSL4. Conclusions: The present study revealed a novel molecular mechanism underlying SAL-induced neurotoxicity via induction of ferroptosis in PD, and uncovered a new pharmacological effect against PD through inhibiting ferroptosis. This study highlights SAL-induced neurotoxicity via ferroptosis as a potential therapeutic target in PD.https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL26679parkinson’s diseasesalsolinolferroptosisacteosideneuroprotection |
| spellingShingle | Hongquan Wang Shuang Wu Qiang Li Huiyan Sun Yumin Wang Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models Frontiers in Bioscience-Landmark parkinson’s disease salsolinol ferroptosis acteoside neuroprotection |
| title | Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models |
| title_full | Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models |
| title_fullStr | Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models |
| title_full_unstemmed | Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models |
| title_short | Targeting Ferroptosis: Acteoside as a Neuroprotective Agent in Salsolinol-Induced Parkinson’s Disease Models |
| title_sort | targeting ferroptosis acteoside as a neuroprotective agent in salsolinol induced parkinson s disease models |
| topic | parkinson’s disease salsolinol ferroptosis acteoside neuroprotection |
| url | https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL26679 |
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