Elimination of Amyloid beta Neurotoxicity.
Aggregation of the Alzheimer amyloid beta peptide (Abeta) Abeta1-42 forms neurotoxic fibrils. In contact with human neurons the fibrils cause rapid influx of external calcium through AMPA/kainate-channels. If this molecular mechanism reflects in vivo events, it could explain the pathogenesis of Alzheimer's disease; activation of AMPA/kainate channels is therefore a likely target for therapeutic intervention. Here we show that short antagonistic "decoy peptides", made of D-amino acids, eliminate this "calcium effect" of Ab1-42. Since chronically elevated calcium levels in the disease trigger activation of pathways that lead to neuron dysfunction and cell death, our decoy peptides are obvious candidates for drug development.
Blanchard
Barbara J.
BJ
Hiniker
Anne E.
AE
Lu
Connie C.
CC
Margolin
Yelena
Y
Yu
Amy S.
AS
Ingram
Vernon M.
VM