A small molecule 20C from Gastrodia elata inhibits α-synuclein aggregation and prevents progression of Parkinson's disease
© 2023. The Author(s)..
Parkinson's disease (PD) is pathologically manifested by the aggregation of α-synuclein, which has been envisioned as a promising disease-modifying target for PD. Here, we identified 20C, a bibenzyl compound derived from Gastrodia elata, able to inhibit the aggregation of A53T variants of α-synuclein directly in vitro. Computational analysis revealed that 20C binds to cavities in mature α-synuclein fibrils, and it indeed displays a strong interaction with α-synuclein and reduced their β-sheet structure by microscale thermophoresis and circular dichroism, respectively. Moreover, incubating neural cells with 20C reduced the amounts of α-synuclein inclusions significantly. The treatment of A53T α-Syn transgenic mice with 20C significantly reduces the toxic α-synuclein levels, improves behavioral performance, rescues dopaminergic neuron, and enhances functional connections between SNc and PD associated brain areas. The transcriptome analysis of SNc demonstrated that 20C improves mitochondrial dynamics, which protects mitochondrial morphology and function against α-synuclein induced degeneration. Overall, 20C appears to be a promising candidate for the treatment of PD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:14 |
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| Enthalten in: |
Cell death & disease - 14(2023), 9 vom: 06. Sept., Seite 594 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peng, Ye [VerfasserIn] |
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| Links: |
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| Themen: |
Alpha-Synuclein |
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| Anmerkungen: |
Date Completed 08.09.2023 Date Revised 21.09.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41419-023-06116-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361715137 |
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| 245 | 1 | 2 | |a A small molecule 20C from Gastrodia elata inhibits α-synuclein aggregation and prevents progression of Parkinson's disease |
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| 500 | |a Date Revised 21.09.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Parkinson's disease (PD) is pathologically manifested by the aggregation of α-synuclein, which has been envisioned as a promising disease-modifying target for PD. Here, we identified 20C, a bibenzyl compound derived from Gastrodia elata, able to inhibit the aggregation of A53T variants of α-synuclein directly in vitro. Computational analysis revealed that 20C binds to cavities in mature α-synuclein fibrils, and it indeed displays a strong interaction with α-synuclein and reduced their β-sheet structure by microscale thermophoresis and circular dichroism, respectively. Moreover, incubating neural cells with 20C reduced the amounts of α-synuclein inclusions significantly. The treatment of A53T α-Syn transgenic mice with 20C significantly reduces the toxic α-synuclein levels, improves behavioral performance, rescues dopaminergic neuron, and enhances functional connections between SNc and PD associated brain areas. The transcriptome analysis of SNc demonstrated that 20C improves mitochondrial dynamics, which protects mitochondrial morphology and function against α-synuclein induced degeneration. Overall, 20C appears to be a promising candidate for the treatment of PD | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Ye, Jun-Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Sha-Sha |e verfasserin |4 aut | |
| 700 | 1 | |a He, Wen-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Zhong-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Hong-Shuo |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Shi-Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Zhao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Nai-Hong |e verfasserin |4 aut | |
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