| Autor: |
Wenqian, Wang, Xinyu, Wang, Wen, Gao, Zhan, Cui, Huitu, Zhang, Fuping, Lu, Fufeng, Liu |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
International Journal of Biological Macromolecules. 211:580-591 |
| ISSN: |
0141-8130 |
| DOI: |
10.1016/j.ijbiomac.2022.05.045 |
| Popis: |
Misfolding and aggregation of α-synuclein (α-syn) play a key role in the pathogenesis of Parkinson's disease (PD). Herein, the inhibitory effect of ulvan on α-syn fibrillogenesis was studied using thioflavin T fluorescence and atomic force microscope assays. It is shown that ulvan could inhibit α-syn fibrillogenesis in a dose-dependent manner. Based on the circular dichroism results, it is found that ulvan delays greatly the conformational transition from its initial random coil to β-sheet rich structure. The protective effect of ulvan against celllular death induced by α-syn aggregates was investigated by MTT colorimetric and cellular staining methods. It is found that ulvan protects greatly PC12 cells from α-syn fibril-induced cytotoxicity. In addition, ulvan disaggregates preformed α-syn fibrils and reduces cytotoxicity in a dose-dependent manner. Thereafter, the inhibitory effects of ulvan against α-syn fibrillogenesis were probed using Caenorhabditis elegans model NL5901 expressing human α-syn. It is found that ulvan extends the lifespan of NL5901 and recovers the lipid deposition by reducing the accumulation of α-syn. Finally, the molecular interactions between ulvan and α-syn pentamer was also explored using molecular docking. These findings suggest that ulvan can be pursued as a novel candidate drug for treatment of PD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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