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Updated: Sep 11, 2025
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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
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Lacmoid-Induced Conformational Changes Inhibit Fibrillation of Human Islet Amyloid Polypeptide
Charu Thapliyal1, Prachi Joshi1, Masochon Raingam1
1School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.
Chembiochem : a European Journal of Chemical Biology
|August 14, 2025
Summary
Lacmoid effectively prevents human islet amyloid polypeptide (IAPP) from forming toxic amyloid fibrils, a key factor in type 2 diabetes. This compound also breaks down existing fibrils and reduces cell toxicity, offering a potential therapeutic strategy.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Type 2 diabetes is a global metabolic disorder linked to pancreatic beta-cell dysfunction.
- Amyloid deposits of human islet amyloid polypeptide (IAPP) are implicated in beta-cell failure.
- IAPP misfolding and aggregation into toxic fibrils contribute to disease pathogenesis.
Purpose of the Study:
- To investigate the potential of lacmoid as an inhibitor of IAPP fibrillation.
- To determine lacmoid's efficacy in disaggregating preformed IAPP fibrils.
- To assess lacmoid's impact on IAPP fibril-induced cytotoxicity.
Main Methods:
- Thioflavin T fluorescence assays to monitor fibrillation.
- Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) for morphological analysis.
- Circular Dichroism (CD) and Fourier Transform Infrared Spectroscopy (FTIR) for structural changes.
- Cytotoxicity assays in U2OS cells and molecular docking studies.
Main Results:
- Lacmoid completely inhibited IAPP fibrillation and disaggregated existing fibrils at equimolar concentrations.
- Significant alterations in IAPP secondary structure were observed in the presence of lacmoid.
- Lacmoid significantly reduced the toxicity of IAPP fibrils in cellular assays.
- Molecular docking identified Asn14 of IAPP as critical for lacmoid interaction.
Conclusions:
- Lacmoid is a potent inhibitor of IAPP fibrillation and a disaggregator of IAPP amyloid fibrils.
- Lacmoid demonstrates protective effects against IAPP fibril-induced cytotoxicity.
- Lacmoid shows promise as a potential therapeutic agent for type 2 diabetes treatment.
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