Back to Search
Start Over
Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson’s disease
- Source :
- Scientific Reports, Vol 12, Iss 1, Pp 1-11 (2022), Scientific Reports
- Publication Year :
- 2022
- Publisher :
- Nature Portfolio, 2022.
-
Abstract
- 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.
- Subjects :
- Parkinson's disease
Science
Protein Aggregation, Pathological
Article
Animals, Genetically Modified
Antiparkinson Agents
Protein Aggregates
mental disorders
Animals
Humans
Benzothiazoles
Caenorhabditis elegans
Caenorhabditis elegans Proteins
Neurons
Multidisciplinary
Drug Repositioning
High-throughput screening
Parkinson Disease
High-Throughput Screening Assays
nervous system diseases
Mice, Inbred C57BL
Disease Models, Animal
Spectrometry, Fluorescence
nervous system
alpha-Synuclein
Medicine
Biological Assay
Tannins
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....5b909fd755913cf9599106599d465ea0