Membrane perturbation by the neurotoxic Alzheimer amyloid fragment beta 25-35 requires aggregation and beta-sheet formation.
The beta-amyloid peptide (beta AP) is a major proteinaceous component of senile plaques and cerebrovascular amyloid deposits found in the brain of patients with Alzheimer's disease. beta AP is reported to be neurotoxic only when it forms beta-sheet structure and aggregates. In the present study, we report that the neurotoxic core of beta AP, beta AP-25-35 (beta 25-35), perturbs liposome membranes, induces membrane current, and exhibits hemolytic activity only in a buffer condition where the peptide forms beta-sheet structure and spontaneously aggregates. In contrast, beta 25-35 in its monomeric random coil structure does not perturb lipid membranes significantly, and exhibits no hemolytic activity. Also, the membrane current was inhibited by Congo Red. The ability of beta 25-35 to interact with membranes highly correlates with its neurotoxicity reported previously. These results suggest that membrane perturbation by aggregated beta 25-35 constitutes the molecular basis of the peptide's neurotoxicity.
Hirakura
Y
Y
School of Pharmaceutical Sciences, University of Tokyo, Japan. yhirakura@mednet.ucla.edu
Satoh
Y
Y
Hirashima
N
N
Suzuki
T
T
Kagan
B L
BL
Kirino
Y
Y
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006461:Hemolysis; D008051:Lipid Bilayers; D008564:Membrane Potentials; D010446:Peptide Fragments / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35)