Apelin-36 mediates neuroprotective effects by regulating oxidative stress, autophagy and apoptosis in MPTP-induced Parkinson’s disease model mice
Abstract
Parkinson's disease (PD), a common human neurodegenerative disorder, is characterized by the presence of intraneuronal Lewy bodies composed principally of abnormal aggregated and post-translationally modified α-synuclein. In our previous research, we have demonstrated the neuroprotective effect of Apelin-36, a neuroendocrine peptide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP)-lesioned PD model mice. Therefore, this study was designed to evaluate the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice. The results showed that MPTP-induced the depletion of dopamine in the striatum (STR) was partially reversed by Apelin-36. Apelin-36 also improved the activity of antioxidant system including superoxide dismutase (SOD) and glutathione (GSH), and decreased the overproduction of malondialdehyde (MDA) in the substantia nigra pars compacta (SNpc) and STR of MPTP-treated mice. Moreover, Apelin-36 downregulated inducible nitric oxide synthase (iNOS) and nitrated α-synuclein expression. Furthermore, Apelin-36 significantly promoted autophagy indicated by the up-regulation of LC3-II and Beclin1 and inhibition of p62 expression in the SNpc and STR of MPTP-treated mice. The protective effect of Apelin-36 was also associated with the inhibition of the apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal kinase (JNK) signaling pathway and inactivation of caspase-3. Taken together, our findings demonstrated that the neuroprotective mechanism of Apelin-36 against MPTP-induced neurotoxicity in mice might be related to decreasing the aggregation of nitrated α-synuclein and alleviating oxidative stress as well as promoting autophagy and inhibiting ASK1/JNK/caspase-3 apoptotic pathway, which provides a novel strategy for PD treatment.
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iNOS expression is enhanced in multiple PD animal models induced by 6-OHDA, MPTP, and aSyn oligomers.
“In addition, iNOS expression was also found to be enhanced in multiple PD animal models induced by 6-OHDA,461 MPTP,462 and aSyn oligomers.463”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [462]
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- Authors
- Zhu, J., Gao, W., Shan, X., Wang, C., Wang, H., Shao, Z., Dou, S., Jiang, Y., Wang, C., & Cheng, B.
- Affiliations
- Shandong University (CN)
- Jining Medical University (CN)
- Corresponding author
- Wang, Chuangong
- Cheng, Baohua
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 1726
- Pages
- 146493
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2978314883
- Cited by
- 65
- References
- 68
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 12 · 2023: 13 · 2022: 11 · 2021: 11 · 2020: 8
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shandong Province (ZR2018Pc011, ZR2014HL040, ZR2010HL057)
- Jining Medical University (JYP201708)
- National Natural Science Foundation of China (81671276, 81501018)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pharmacology › Apelin-related biomedical research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- apelin-36, Parkinson's disease, MPTP-induced neurotoxicity, neuroprotection, oxidative stress, autophagy, apoptosis, dopamine depletion, substantia nigra pars compacta, striatum, caspase-3, inducible nitric oxide synthase, superoxide dismutase
- MeSH terms
- Apelin, Animals, Autophagy, Corpus Striatum, Disease Models, Animal, Dopamine, Gene Expression Regulation, Male, Mice, Inbred C57BL, Signal Transduction, Oxidative Stress, Neuroprotective Agents, MPTP Poisoning, Pars Compacta
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