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Updated: Sep 20, 2025
A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
Fatty acid-based polymeric micelles to ameliorate amyloidogenic disorders
Avisek Bera1, Debangana Mukhopadhyay2, Kalyan Goswami3
1Polymer Research Centre and Centre for Advanced Functional Materials, Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur - 741246, Nadia, West Bengal, India. pgk89@iiserkol.ac.in.
Researchers developed fatty acid-tethered block copolymers (FABC) to inhibit insulin amyloid fibrils, a key factor in diabetes. Stearic acid-based micelles significantly reduced fibril formation and toxicity, offering a novel therapeutic approach.
Area of Science:
- Polymer Chemistry
- Biophysical Chemistry
- Materials Science
Background:
- Amyloidogenic protein aggregation, particularly insulin fibrillation, is implicated in diabetes pathogenesis.
- Developing effective inhibitors against amyloid formation is crucial for therapeutic intervention.
Purpose of the Study:
- To synthesize and evaluate amphiphilic block copolymers with fatty acid (FA) moieties as anti-amyloidogenic agents.
- To investigate the role of FA pendants in modulating insulin fibrillation using various biophysical techniques.
Main Methods:
- Reversible addition fragmentation chain-transfer (RAFT) polymerization for copolymer synthesis.
- Formation of FABC micelles and assessment of their impact on insulin fibrillation kinetics.
- Circular dichroism spectroscopy to analyze conformational changes and β-sheet content.
- Evaluation of fibril disintegration and reduction of fibril-induced toxicity.
- Theoretical simulations to support experimental findings.
Main Results:
- FABC micelles significantly prolonged the lag phase of insulin fibrillation, with stearic acid-based micelles (SABC475) showing the most pronounced effect.
- Circular dichroism confirmed that FABC micelles reduce β-sheet content, inhibiting fibril formation.
- FABC micelles effectively disintegrated mature insulin fibrils and diminished fibril-induced toxicity.
- Hydrophobic interactions and hydrogen bonding were identified as key mechanisms driving inhibition.
Conclusions:
- Fatty acid-tethered block copolymers are effective inhibitors of insulin fibrillation.
- The developed polymeric micelles offer a promising strategy for developing novel anti-amyloidogenic therapeutics for diabetes treatment.
