Identification of amyloid-ß binding sites using an antisense peptide approach

Abstract

The amyloid-[beta] (A[beta]) peptide is a cytotoxic peptide implicated in the pathology of Alzheimer's disease (AD). Catalase and the endoplasmic reticulum A[beta] binding dehydrogenase (ERAB) are both inhibited by characterized fragments of the A[beta] peptide. In order to target such proteins it is essential to determine which components of these enzymes interact with A[beta]. This study reports the use of antisense peptide methodology to identify specific A[beta]-binding domains. Synthetic peptides corresponding to the regions of catalase and ERAB identified showed specific binding to A[beta] and also prevented A[beta] cytotoxicity. Antisense peptide methodology has identified A[beta] recognition sequences and may also be applied to the identification of novel A[beta] protein interactions to identify targets for use in the treatment of AD.