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(Received for publication, August 9, 1996, and in revised form, September 19, 1996)
From the Division of Neuroscience and Department of Psychiatry,
UCLA School of Medicine, Neuropsychiatric Institute, Brain Research
Institute, University of California, Los Angeles, California 90024-1759 and the West Los Angeles Veterans' Administration Medical Center, Los
Angeles, California 90024
Prions cause neurodegenerative disease in animals
and humans. Recently it was shown that a 21-residue fragment of the
prion protein (106-126) could be toxic to cultured neurons. We report here that this peptide forms ion-permeable channels in planar lipid
bilayer membranes. These channels are freely permeable to common
physiological ions, and their formation is significantly enhanced by
"aging" and/or low pH. We suggest that channel formation is the
cytotoxic mechanism of action of amyloidogenic peptides found in
prion-related encephalopathies and other amyloidoses. The channels
reported here are large enough and nonselective enough to mediate cell
death through discharge of cellular membrane potential, changes in
ionic homeostasis, and specifically, influx of calcium, perhaps
triggering apoptosis.
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