Aptamer-Based DNAAssembly for Detecting Zn2+ and Inhibiting Amyloid β Aggregation
【摘要】：Alzheimer ' s disease(AD) is one of the most common age-related neurodegenerative diseases in which abundant amyloid β(Aβ) aggregates come into being neuritic plaques in the brain. In accordance with previous amyloid cascade hypothesis, the aggregation of Aβ in plaques is the primary driving force for AD pathogenesis.[2,3,4] In amyloid neurotoxic plaques, the homeostasis of metal ions,particularly zinc ion(Zn~(2+)), is seriously damaged. Therefore, reasonable design of Zn~(2+)-targeted therapeutic agents is crucial for understanding Zn~(2+)-A β-related neuropathology and for further realization of Zn~(2+)-binding therapy for AD. Herein, we developed a molecular recognition-based DNA assembly for detecting Zn~(2+) around Aβ and further inhibiting Zn~(2+)-mediated Aβ aggregation. The DNA assembly can selectively target A β species and block the surrounding Zn~(2+) due to the specific recognition capability of aptamers. More importantly, this DNA assembly can inhibit the generation of Zn~(2+)-triggered Aβ aggregation due to the trapping of Zn~(2+) around Aβ species. These functions make this molecular recognition-based DNA assembly a promising platform for understanding Zn~(2+)-A β-related neuropathology and manipulating aggregation of A β in AD. Our approach can provide valuable information for studying the Zn~(2+)-A β-related neuropathology and exhibits great potential for AD treatment.