Related Experiment Video
Updated: Apr 23, 2026
09:44
Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
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Angelic Acid Disassembles Fibrillar α-Synuclein Aggregates through β-Sheet Interface Disruption
Hyo Gi Jung1, Junho Bang1,2,3, Juhyun Kim4
1School of Biomedical Engineering, College of Health Science, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.
ACS Chemical Neuroscience
|April 21, 2026
Summary
Angelic acid effectively disassembles pathological alpha-synuclein fibrils, reducing neurotoxic protein accumulation and cytotoxicity in cellular models of synucleinopathies like Parkinson's disease.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Pathological aggregation of alpha-synuclein (αS) is a key feature of synucleinopathies, including Parkinson's disease.
- Fibrillar αS aggregates are implicated in driving neurodegeneration in these conditions.
Purpose of the Study:
- To identify small molecules that can disassemble fibrillar αS aggregates.
- To evaluate the therapeutic potential of identified compounds for synucleinopathies.
Main Methods:
- Screening of a natural product library using a plasmonic nanoparticle amyloid corona platform.
- Physicochemical property analysis for cell permeability and CNS accessibility.
- Characterization of αS fibril disruption using spectroscopy and microscopy.
- In vitro cell-based assays to assess αS reduction and cytotoxicity.
Main Results:
- Angelic acid was identified as a top candidate for its ability to disrupt β-sheet rich conformations and fragment αS fibrils.
- Molecular docking suggested interactions between angelic acid and αS fibril interfaces.
- Angelic acid significantly reduced intracellular αS accumulation (up to 91.4%) and alleviated αS fibril-induced cytotoxicity (34.1%) in a cellular model.
Conclusions:
- Angelic acid demonstrates potent αS-targeting activity, reducing toxic aggregates and cytotoxicity.
- Angelic acid represents a promising lead compound for synucleinopathy treatment.
- Further in vivo studies are warranted to evaluate angelic acid's efficacy in synucleinopathy models.
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