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Updated: May 20, 2026
15:04
Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
What does make an amyloid toxic: morphology, structure or interaction with membrane?
Karine Berthelot1, Christophe Cullin, Sophie Lecomte
1Laboratoire de Chimie des Polymères Organiques, LCPO CNRS UMR 5629, ENSCBP - IPB, Pessac, France.
Biochimie
|July 25, 2012
Summary
Amyloid toxicity is linked to intermediate structures interacting with cell membranes. Antiparallel beta-sheet oligomers and fibers disrupt membranes, potentially forming pores and causing toxicity.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Amyloid toxicity is a significant research area, often linked to intermediate structures and membrane interactions.
- Membrane composition and lipid charge can influence amyloid formation and toxicity.
- Characterizing amyloid intermediates and their membrane interaction mechanisms remains challenging due to analytical limitations.
Purpose of the Study:
- To review in vitro characteristics contributing to amyloid toxicity.
- To compare the behavior of a non-toxic amyloid (HET-s) with a toxic mutant (M8).
- To elucidate mechanisms of amyloid-membrane interactions.
Main Methods:
- In vitro characterization of amyloid structures and their interactions.
- Comparative analysis of a model non-toxic amyloid and its toxic mutant.
- Review of recent evidence on amyloid oligomer formation and membrane disruption.
Main Results:
- Short oligomers and/or fibers assembled in antiparallel beta-sheets strongly interact with and disrupt membranes.
- Evidence suggests toxic oligomers form antiparallel beta-helices, capable of pore formation.
- A novel "raft-like" insertion model for amyloid-membrane interaction is proposed.
Conclusions:
- Antiparallel beta-sheet structures in amyloid oligomers and fibers are key to membrane disruption and toxicity.
- Amyloid-induced membrane destabilization may occur via pore formation or a "raft-like" insertion mechanism.
- Further research is needed to fully characterize amyloid intermediates and their toxic mechanisms at membranes.
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