Elimination of Amyloid beta Neurotoxicity

J Alzheimers Dis. 2000 Jun;2(2):137-149. doi: 10.3233/jad-2000-2214.

Abstract

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.