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 su
ggest that channel formation is the cytotoxic mechanism of action of a
myloidogenic peptides found in prion-related encephalopathies and othe
r amyloidoses. The channels reported here are large enough and nonsele
ctive enough to mediate cell death through discharge of cellular membr
ane potential, changes in ionic homeostasis, and specifically, influx
of calcium, perhaps triggering apoptosis.