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Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
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Two-step screening method to identify α-synuclein aggregation inhibitors for Parkinson's disease
Makoto Hideshima1, Yasuyoshi Kimura1, César Aguirre1
1Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Scientific Reports
|January 11, 2022
Summary
Researchers screened FDA-approved compounds to find treatments for Parkinson's disease. Tannic acid effectively inhibited alpha-synuclein aggregation, showing promise as a disease-modifying therapy.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Parkinson's disease involves toxic alpha-synuclein aggregation in neurons.
- Current therapies do not modify disease progression.
- Inhibiting alpha-synuclein aggregation is a key therapeutic strategy.
Purpose of the Study:
- To identify novel inhibitors of alpha-synuclein aggregation.
- To screen FDA-approved small compounds for potential Parkinson's disease treatments.
- To validate promising candidates in cellular and organismal models.
Main Methods:
- A two-step screening process was employed, starting with a thioflavin T assay.
- The second step utilized a cell-based assay to assess aggregation inhibition and toxicity.
- Validated hits using primary neuronal and Caenorhabditis elegans models.
Main Results:
- 1262 FDA-approved compounds were screened, identifying 30 potential inhibitors.
- Seven compounds demonstrated efficacy in preventing alpha-synuclein aggregation without significant toxicity.
- Tannic acid emerged as the most potent inhibitor, validated in neuronal and C. elegans models.
Conclusions:
- The developed two-step screening system effectively identifies alpha-synuclein aggregation inhibitors.
- Tannic acid is a promising candidate for developing disease-modifying therapies for Parkinson's disease.
