The insect molting hormone 20-hydroxyecdysone protects dopaminergic neurons against MPTP-induced neurotoxicity in a mouse model of Parkinson’s disease
Abstract
20-hydroxyecdysone (20E), a steroidal prohormone, is secreted from the prothoracic glands. While 20E has been shown to have neuroprotective effects in Parkinson's disease (PD) models in vitro, its effects have not yet been examined in vivo. We sought to assess the behavioral and mechanistic effects of 20E on MPTP-induced toxicity in mice. To this end, we used behavioral tests, stereological analyses of dopaminergic neurons by tyrosine hydroxylase immunohistochemistry, and assessments of apoptotic mechanisms, focusing on Nrf2 signaling through Western blotting and ELISA assays. A 20E treatment protected against MPTP-induced motor incoordination, postural imbalance, and bradykinesia, and significantly reduced dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc) and the striatum (ST). It also attenuated dopamine deficiency in the ST, modulated levels of antioxidative enzymes superoxide dismutase, catalase, and glutathione in the SNpc, increased the Bcl-2/Bax ratio, and inhibited cytosolic cytochrome c release and caspase-9, -7, and -3 activity in the SNpc. These results indicated that 20E inhibited the apoptotic cascade. Furthermore, the attenuation of MPTP neurotoxicity was associated with inhibited cleaved-caspase signaling pathways, along with upregulated Nrf2 pathways in the SNpc, suggesting that 20E mitigates MPTP-induced neurotoxicity via mitochondria-mediated apoptosis by modulating anti-oxidative activities. Our results suggest that 20E can inhibit MPTP-induced behavioral and neurotoxic effects in mice. This lays the foundation for further research on 20E as a potential target for therapeutic use.
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In a mouse model of Parkinson disease, 20E protected dopaminergic neurones, mitigating mitochondria-mediated apoptosis and inducing anti-oxidant enzymes (SOD, catalase, GTHpx, and GR).
“In a mouse model of Parkinson disease, 20E protected dopaminergic neurones, mitigating mitochondria-mediated apoptosis and inducing anti-oxidant enzymes (SOD, catalase, GTHpx, and GR).”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [50]
20E increased the Bcl2/Bax ratio and decreased cytochrome C release and caspase activities with increased activity of the Nrf2 pathway.
“It also increased the Bcl2/Bax ratio and decreased cytochrome C release and caspase activities with increased activity of the Nrf2 (phosphoinositide-3-kinase-nuclear factor E2-related factor 2) pathway.”
From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [50]
20E has adaptogenic, anabolic, antioxidant, hepato-, cardio-, and neuroprotective activities in healthy non-cancer tissues.
“because of its adaptogenic, anabolic, antioxidant, hepato-, cardio-, and neuroprotective activities in healthy non-cancer tissues [3,5,7,9]”
From 20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells (2024) · cites this paper as [5]
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“This showed the 20E protected against neurotoxicity by its anti-apoptotic and anti-oxidant capacity and may have a potential in the therapy of Parkinson disease [50].”
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- Authors
- Lim, H.-S., Moon, B. C., Lee, J., Choi, G., & Park, G.
- Affiliations
- Korea Institute of Oriental Medicine (KR)
- Corresponding author
- Park, Gunhyuk
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 159
- Pages
- 23-36
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W3046596834
- Cited by
- 30
- References
- 60
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 1 · 2023: 7 · 2022: 9 · 2021: 3
- FWCI
- 2.05
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Korea Institute of Oriental Medicine
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- 20-hydroxyecdysone, MPTP-induced neurotoxicity, Parkinson's disease, dopaminergic neurons, neuroprotection, substantia nigra pars compacta, striatum, apoptosis, mitochondrial apoptosis, Nrf2 signaling, oxidative stress, caspase activation, dopamine deficiency, insect molting hormone
- MeSH terms
- Animals, Disease Models, Animal, Ecdysone, Ecdysterone, Insecta, Mice, Inbred C57BL, Parkinson Disease, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Neuroprotective Agents, MPTP Poisoning, Mice, Dopaminergic Neurons
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