A Red-Emitting Fluorescent Probe for Visualizing Hydroxyl Radical in Parkinson’s Disease and Guiding the Discovery of Methyl Ferulate for Therapeutic Intervention

Parkinson's disease (PD) is pathologically linked to oxidative stress induced by reactive oxygen species (ROS). However, the role of the most deleterious ROS, ^•OH, in PD progression remains elusive due to the lack of effective tools for real time imaging in the brain. Herein, we developed a red-emitting fluorescent probe, DCM-HR, for specific and sensitive detection of ^•OH. Cell imaging studies revealed DCM-HR could dynamically track elevated ^•OH levels under Fe²⁺-induced oxidative stress, during ferroptosis in PD progression, and in PD model cells and mice. Utilizing DCM-HR as a screening tool, we discovered methyl ferulate as a potent ^•OH scavenger capable of alleviating PD symptoms in vivo. Importantly, it was revealed that the overproduction of ^•OH during ferroptosis was found to be strongly associated with PD progression.