A simple and label-free electrochemical method for detection of beta-site amyloid precursor protein cleaving enzyme and screening of its inhibitor

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is an aspartic protease that promotes the production of beta-amyloid (A beta) peptides from beta-site amyloid precursor protein. Pharmacological reduction of A beta production by inhibiting BACE1 has emerged as a promising target for the treatment of Alzheimer's disease (AD). In this work, we reported a simple electrochemical method for detection of BACE1 and screening of its inhibitor. This method made use of an unlabeled peptide that comprises a segment of beta-site amyloid precursor protein with the Swiss mutation. The peptide-heme complex formed on the electrode surface showed strong electrocatalytic O-2 reduction. Cleavage of the peptide by BACE1 detached the heme-binding fragment from the electrode surface, leading to a remarkable decrease in the electrochemical signal. Suppression of BACE1 by the inhibitor yielded a larger voltammetric signal. The IC50 of the inhibitor tested by this method (15.7 nM) was in agreement with that reported. The proposed method could serve as a promising alternative to the traditional methods for probing of BACE1 activity and screening of BACE1 inhibitor owing to its simplicity, high sensitivity and low assay cost. (C) 2015 Elsevier B.V. All rights reserved.