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

The amyloid-beta (A beta) peptide is a cytotoxic peptide implicated in the pathology of Alzheimer's disease (AD). Catalase and the endoplasmic reticul um A beta binding dehydrogenase (ERAB) are both inhibited by characterized fragments of the A beta peptide. In order to target such proteins it is ess ential to determine which components of these enzymes interact with A beta. This study reports the use of antisense peptide methodology to identify sp ecific A beta -binding domains. Synthetic peptides corresponding to the reg ions of catalase and ERAB identified showed specific binding to A beta and also prevented A beta cytotoxicity. Antisense peptide methodology has ident ified A beta recognition sequences and may also be applied to the identific ation of novel A beta protein interactions to identify targets for use in t he treatment of AD. NeuroReport 12:2561-2566 (C) 2001 Lippincott Williams & Wilkins.