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

作者：Xia Ning; Zhang Youjuan; Guan Pengpeng; Hao Yuanqiang; Liu Lin^*

来源：Sensors and Actuators B: Chemical , 2015, 213: 111-115.

DOI：10.1016/j.snb.2015.02.081

• Alzheimer's disease
• Beta-amyloid
• BACE1 inhibitor
• Electrocatalysis
• Heme

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.

• 出版日期2015-7-5
• 单位安阳师范学院; 商丘师范学院