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 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.
Milton
N G
NG
Department of Molecular Pathology and Clinical Biochemistry, Royal Free and University College Medical School, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.
Mayor
N P
NP
Rawlinson
J
J
D015094:3-Hydroxyacyl CoA Dehydrogenases; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016375:Antisense Elements (Genetics); D001665:Binding Sites / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016375:Antisense Elements (Genetics); D002352:Carrier Proteins; D010446:Peptide Fragments; C098994:amyloid beta-protein (1-43); D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C458480:Hsd17b10 protein, mouse; D002374:Catalase