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Updated: Nov 29, 2025

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
The human islet amyloid polypeptide in protein misfolding disorders: Mechanisms of aggregation and interaction with
Adam El Saghir1, Gianluca Farrugia1, Neville Vassallo1
1Dept. of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Centre for Molecular Medicine and Biobanking, University of Malta, Msida, Malta.
Abstract:
Human islet amyloid polypeptide (hIAPP), otherwise known as amylin, is a 37-residue peptide hormone which is reported to be a common factor in protein misfolding disorders such as type-2 diabetes mellitus, Alzheimer's disease and Parkinson's disease, due to deposition of insoluble hIAPP amyloid in the pancreas and brain. Multiple studies point to the importance of the peptide's interaction with biological membranes and the cytotoxicity of hIAPP species. Here, we discuss the aggregation pathways of hIAPP amyloid fibril formation and focus on the complex interplay between membrane-mediated assembly of hIAPP and the associated mechanisms of membrane damage caused by the peptide species. Mitochondrial membranes, which are unique in their lipid composition, are proposed as prime targets for the early intracellular formation of hIAPP toxic entities. We suggest that future studies should include more physiologically-relevant and in-cell studies to allow a more accurate model of in vivo interactions. Finally, we underscore an urgent need for developing effective therapeutic strategies aimed at hindering hIAPP-phospholipid interactions.
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