| Autor: |
Hideshima, Makoto, Kimura, Yasuyoshi, Aguirre, César, Kakuda, Keita, Takeuchi, Toshihide, Choong, Chi-Jing, Doi, Junko, Nabekura, Kei, Yamaguchi, Keiichi, Nakajima, Kichitaro, Baba, Kousuke, Nagano, Seiichi, Goto, Yuji, Nagai, Yoshitaka, Mochizuki, Hideki, Ikenaka, Kensuke |
| Předmět: |
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| Zdroj: |
Scientific Reports; 1/10/2022, Vol. 12 Issue 1, p1-11, 11p |
| Abstrakt: |
Parkinson's disease is a neurodegenerative disease characterized by the formation of neuronal inclusions of α-synuclein in patient brains. As the disease progresses, toxic α-synuclein aggregates transmit throughout the nervous system. No effective disease-modifying therapy has been established, and preventing α-synuclein aggregation is thought to be one of the most promising approaches to ameliorate the disease. In this study, we performed a two-step screening using the thioflavin T assay and a cell-based assay to identify α-synuclein aggregation inhibitors. The first screening, thioflavin T assay, allowed the identification of 30 molecules, among a total of 1262 FDA-approved small compounds, which showed inhibitory effects on α-synuclein fibrilization. In the second screening, a cell-based aggregation assay, seven out of these 30 candidates were found to prevent α-synuclein aggregation without causing substantial toxicity. Of the seven final candidates, tannic acid was the most promising compound. The robustness of our screening method was validated by a primary neuronal cell model and a Caenorhabditis elegans model, which demonstrated the effect of tannic acid against α-synuclein aggregation. In conclusion, our two-step screening system is a powerful method for the identification of α-synuclein aggregation inhibitors, and tannic acid is a promising candidate as a disease-modifying drug for Parkinson's disease. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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