A superior near infrared fluorescent probe for revealing the relationship between peroxynitrite and Alzheimer's disease

The typical neurodegenerative Alzheimer's disease (AD) poses an increasing threat to human health as the population ages. Though increasing attention has been drawn for the etiology of AD over decades, regretfully, the exact pathogenesis of AD is not fully elucidated. The elevated levels of ROS are among the major pathological alterations in AD. Among them, peroxynitrite (ONOO-) exhibits a greater impact compared to other reactive oxygen species and plays an important role in AD, but the role ONOO- plays in AD progression remains unclear. In this work, the near-infrared (NIR) fluorophore (benzopyran derivative) was optimized by molecular skeleton modification, and a fluorophore DCM-Cl-OH with better spectral properties was obtained. On this basis, a NIR fluorescence probe DCM-Cl-P with excellent detection performance was obtained. Based on the high selectivity and fast response of the probe to ONOO-, DCM-Cl-P was used to visual detection of ONOO- in living cells and zebrafish, and further demonstrated the excessive accumulation of ONOO- in AD model mice. More importantly, through analysis of the correlation between ONOO- and amyloid-β protein (Aβ), ONOO- and the aggregation of Aβ were closely related and mutually reinforcing was demonstrated and ONOO- underwent significant changes in the early stage of the change of Aβ aggregation, indicating that ONOO- may serve as an early marker of AD. These findings have greatly promoted the research on the intrinsic relationship between ONOO- and AD, and provides a powerful means for pathological research of AD.