title: Selective amyloid β oligomer assay based on abasic site-containing molecular beacon and enzyme-free amplification.
abstract: Amyloid-beta (Aβ) oligomers are highly toxic species in the process of Aβ aggregation and are regarded as potent therapeutic targets and diagnostic markers for Alzheimer's disease (AD). Herein, a label-free molecular beacon (MB) system integrated with enzyme-free amplification strategy was developed for simple and highly selective assay of Aβ oligomers. The MB system was constructed with abasic site (AP site)-containing stem-loop DNA and a fluorescent ligand 2-amino-5,6,7-trimethyl-1,8-naphyridine (ATMND), of which the fluorescence was quenched upon binding to the AP site in DNA stem. Enzyme-free amplification was realized by target-triggered continuous opening of two delicately designed MBs (MB1 and MB2). Target DNA hybridization with MB1 and then MB2 resulted in the release of two ATMND molecules in one binding event. Subsequent target recycling could greatly amplify the detection sensitivity due to the greatly enhanced turn-on emission of ATMND fluorescence. Combining with Aβ oligomers aptamers, the strategy was applied to analyze Aβ oligomers and the results showed that it could quantify Aβ oligomers with high selectivity and monitor the Aβ aggregation process. This novel method may be conducive to improve the diagnosis and pathogenic study of Alzheimer's disease.
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Linling
authors.initials: L
authors.lastname: Zhu
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Junying
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Fengyang
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Lu
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China.
authors.forename: Chongchong
authors.initials: C
authors.lastname: Feng
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China. Electronic address: zaxu@chem.ecnu.edu.cn.
authors.forename: Zhiai
authors.initials: Z
authors.lastname: Xu
authors.affiliation: School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241, PR China. Electronic address: wzhang@chem.ecnu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis*; D016229:Amyloid beta-Peptides / Q000302:isolation & purification*; D015374:Biosensing Techniques / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008024:Ligands; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification*; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D010446:Peptide Fragments
keywords: Abasic site; Amyloid β; Aptamer; Molecular beacon; Oligomer