title: Amyloid ion channels: a common structural link for protein-misfolding disease.
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.
authors: Neuroscience Research Institute, University of California, Santa Barbara, CA 93106, USA.
authors: Arjan
authors: A
authors: Quist
authors: Ivo
authors: I
authors: Doudevski
authors: Hai
authors: H
authors: Lin
authors: Rushana
authors: R
authors: Azimova
authors: Douglas
authors: D
authors: Ng
authors: Blas
authors: B
authors: Frangione
authors: Bruce
authors: B
authors: Kagan
authors: Jorge
authors: J
authors: Ghiso
authors: Ratnesh
authors: R
authors: Lal
mesh_terms: D000682:Amyloid / Q000502:physiology*; D000686:Amyloidosis / Q000503:physiopathology*; D002942:Circular Dichroism; D004586:Electrophoresis; D004594:Electrophysiology; D007473:Ion Channels / Q000502:physiology*; D018625:Microscopy, Atomic Force; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000682:Amyloid; D007473:Ion Channels