Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson's disease
Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson's disease using 6-hydroxydopamine. When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease. Next, we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor down-regulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
Neural regeneration research - 18(2023), 5 vom: 27. Mai, Seite 1099-1106 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Hai-Ying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 11.01.2023 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.4103/1673-5374.355815 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347698638 |
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| 100 | 1 | |a Zhang, Hai-Ying |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Neuroprotective effects of insulin-like growth factor-2 in 6-hydroxydopamine-induced cellular and mouse models of Parkinson's disease |
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| 520 | |a Skin-derived precursor Schwann cells have been reported to play a protective role in the central nervous system. The neuroprotective effects of skin-derived precursor Schwann cells may be attributable to the release of growth factors that nourish host cells. In this study, we first established a cellular model of Parkinson's disease using 6-hydroxydopamine. When SH-SY5Y cells were pretreated with conditioned medium from skin-derived precursor Schwann cells, their activity was greatly increased. The addition of insulin-like growth factor-2 neutralizing antibody markedly attenuated the neuroprotective effects of skin-derived precursor Schwann cells. We also found that insulin-like growth factor-2 levels in the peripheral blood were greatly increased in patients with Parkinson's disease and in a mouse model of Parkinson's disease. Next, we pretreated cell models of Parkinson's disease with insulin-like growth factor-2 and administered insulin-like growth factor-2 intranasally to a mouse model of Parkinson's disease induced by 6-hydroxydopamine and found that the level of tyrosine hydroxylase, a marker of dopamine neurons, was markedly restored, α-synuclein aggregation decreased, and insulin-like growth factor-2 receptor down-regulation was alleviated. Finally, in vitro experiments showed that insulin-like growth factor-2 activated the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. These findings suggest that the neuroprotective effects of skin-derived precursor Schwann cells on the central nervous system were achieved through insulin-like growth factor-2, and that insulin-like growth factor-2 may play a neuroprotective role through the insulin-like growth factor-2 receptor/PI3K/AKT pathway. Therefore, insulin-like growth factor-2 may be an useful target for Parkinson's disease treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 6-hydroxydopamine | |
| 650 | 4 | |a Parkinson’s disease | |
| 650 | 4 | |a alpha-synuclein | |
| 650 | 4 | |a insulin-like growth factor-2 | |
| 650 | 4 | |a insulin-like growth factor-2 receptor | |
| 650 | 4 | |a neurodegeneration | |
| 650 | 4 | |a neuroprotection | |
| 650 | 4 | |a skin-derived precursor Schwann cells | |
| 700 | 1 | |a Jiang, Yong-Cheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jun-Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Jia-Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xin-Jue |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Jia-Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Kai-Fu |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Xiao-Su |e verfasserin |4 aut | |
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