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Bile Acids as Modulators of α-Synuclein Aggregation: Implications for Parkinson's Therapy
Harpreet Kaur1, Devansh Swadia2, Sharmistha Sinha1
1Chemical Biology Unit, Institute of Nano Science and Technology, Sector-81, Knowledge City, Sahibzada Ajit Singh Nagar, Mohali 140306, Punjab, India.
ACS Chemical Neuroscience
|October 15, 2024
Summary
Bile acids like lithocholic acid (LCA) accelerate Parkinson's disease (PD) protein aggregation and toxicity. Targeting bile acid metabolism may offer a novel therapeutic strategy for PD.
Area of Science:
- Biochemistry
- Neuroscience
- Molecular Biology
Background:
- Parkinson's disease (PD) involves alpha-synuclein (α-synuclein) aggregation into toxic amyloid fibrils.
- Altered bile acid profiles in PD suggest a potential role in α-synuclein aggregation.
Purpose of the Study:
- To investigate the impact of lithocholic acid (LCA) and deoxycholic acid (DCA) on α-synuclein aggregation and toxicity.
- To elucidate the binding interactions of LCA and DCA with α-synuclein.
Main Methods:
- In vitro aggregation assays and electrophoresis to monitor α-synuclein fibril formation.
- Biochemical binding studies to identify α-synuclein interaction sites.
- Cytotoxicity assays to assess cellular toxicity.
Main Results:
- LCA significantly accelerated α-synuclein aggregation (75% reduction in lag phase) and promoted toxic oligomer formation.
- DCA showed a milder effect on aggregation (30% reduction in lag phase) and interacted with the N-terminal region.
- LCA demonstrated greater promotion of SDS-resistant oligomers and induced lower cell viability compared to DCA.
- Combined LCA and DCA exhibited synergistic effects on aggregation and toxicity.
Conclusions:
- Bile acids, particularly LCA, play a significant role in modulating α-synuclein aggregation and associated toxicity.
- The findings suggest bile acid metabolism as a potential therapeutic target for Parkinson's disease.
- Specific binding interactions of bile acids with α-synuclein influence aggregation pathways.
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