An Efficient Biosensor for Monitoring Alzheimer's Disease Risk Factors: Modulation and Disaggregation of Aβ Aggregation Process
Alzheimer’s Disease (AD) is a progressive neurodegenerative disease, which could lead to a complete loss of cognition. Cu2+ and H2S are both correlated with physiological and pathological events of AD. Therefore, suitable methods to continuously monitor Cu2+ and H2S are in great demand for a better understanding of the detailed mechanism of Alzheimer’s Disease. Based on heteroatoms (N, O, S) competitive effect, a series of reversible “off-on-off” fluorescent probes S1-S3 for detecting Cu2+ and H2S was designed and synthesized, which contain different alkaloids as acceptors. The mechanism is demonstrated by IR, Job’ plot and DFT calculation. Three compounds exhibit high selectivity and sensitivity (limits of detection = 1.95 nM, 1.51 nM, 6.62 nM) for Cu2+ with fast response rate. In addition, S1 has extremely low cytotoxicity and superb membrane permeability, which could be applied in living MCF-7 cells and living mice to monitor Cu2+ under physiological conditions. More importantly, the excellent chelation of probe S1 for Cu2+ was effectively utilized to capture Cu2+from the aggregation of Aβ which was observed by the experiment of ThT fluorescence, transmission electron microscopy (TEM), and native polyacrylamide gel electrophoresis (native-PAGE).