Elimination of Amyloid β Neurotoxicity

Article type: Research Article

Authors: Blanchard, Barbara J. | Hiniker, Anne E. | Lu, Connie C. | Margolin, Yelena | Yu, Amy S. | Ingram, Vernon M.^{; *}

Affiliations: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

Correspondence: [*] Corresponding author: Dr V.M. Ingram, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA, E-mail: [email protected]

Abstract: Aggregation of the Alzheimer amyloid β peptide (Aβ) Ab1-42 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.

DOI: 10.3233/JAD-2000-2214

Journal: Journal of Alzheimer's Disease, vol. 2, no. 2, pp. 137-149, 2000