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Updated: Aug 17, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Amyloid ion channels: a common structural link for protein-misfolding disease
Arjan Quist1, Ivo Doudevski, Hai Lin
1Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
Abstract:
Protein conformational diseases, including Alzheimer's, Huntington's, and Parkinson's diseases, result from protein misfolding, giving a distinct fibrillar feature termed amyloid. Recent studies show that only the globular (not fibrillar) conformation of amyloid proteins is sufficient to induce cellular pathophysiology. However, the 3D structural conformations of these globular structures, a key missing link in designing effective prevention and treatment, remain undefined as of yet. By using atomic force microscopy, circular dichroism, gel electrophoresis, and electrophysiological recordings, we show here that an array of amyloid molecules, including amyloid-beta(1-40), alpha-synuclein, ABri, ADan, serum amyloid A, and amylin undergo supramolecular conformational change. In reconstituted membranes, they form morphologically compatible ion-channel-like structures and elicit single ion-channel currents. These ion channels would destabilize cellular ionic homeostasis and hence induce cell pathophysiology and degeneration in amyloid diseases.
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