Small-molecule fluorescent probes for imaging intracellular amyloid toxicity induces ferroptosis via HClO fluctuation in Alzheimer's disease.

BACKGROUND

Amyloid toxicity induces ferroptosis play a crucial role in the pathological dysfunction of brains affected by Alzheimer's disease (AD). Despite this, brain probing implements for looking into the relationship between ferroptosis and ROS in the brains of AD victims are currently scarce. Herein, a HClO activated ESIPT fluorescent probe HCC-Br was engineered to investigate the complicated correlations between HClO and AD, achieving in vivo diagnosing and evaluating of AD progression.

RESULTS

With this probe, we could also utilize HCC-Br for the visualization and tracking of endogenous HClO production in live cells during Aβ42-induced ferroptosis. More crucially, our findings suggest that tannic acid (TA) shows promise as an effective neuroprotective agent to control MPO-mediated oxidative stress in this stimulated condition. The small molecular structure and suitable lipophilicity endowed HCC-Br with remarkable blood-brain barrier (BBB) permeability, making it enormously applicable to the in vivo detection of HClO variations in AD brains.

SIGNIFICANCE AND NOVELTY: Overall, this study presents a versatile fluorescence tool that can help clarify the contributions of HClO production by MPO in the pathogenic mechanisms of AD. Furthermore, it holds tremendous prospects in exploring the function of HClO in ferroptosis-related pathogenesis and treatment of AD.