A novel NIR fluorescent probe for visualizing hydrogen sulfide in Alzheimer's disease

Abstract

Alzheimer's disease (AD) represents a devastating form of neurodegeneration, hallmarked by a relentless erosion of memory and cognitive faculties. One key player in this complex pathology is hydrogen sulfide (H₂S), a gaseous neurotransmitter that is highly concentrated in the brain. Its fluctuating levels have been compellingly linked to the onset and progression of AD. Despite the availability of numerous fluorescent probes for detecting H₂S, targeted imaging of this neurotransmitter within AD models remains underexplored. To bridge this gap, we have engineered an innovative near-infrared (NIR) “turn-on” fluorescent probe, designated as probe 1. Crafted around a dicyanoisophorone scaffold, the probe incorporates a strategic methoxy modification to facilitate a bathochromic spectral shift. Impressively, upon binding with H₂S, probe 1 exhibited a robust 46-fold enhancement in fluorescence at a wavelength of 680 nm. We successfully deployed this probe to visualize both exogenous and endogenous H₂S in living cells and zebrafish. Further, our pathogenic investigations have corroborated that diminished H₂S levels are intricately linked to an escalation in amyloid plaque formation. Most crucially, we employed probe 1 to capture real-time images of H₂S concentrations within the hippocampal tissue of AD mouse models. This revealed a significant depletion in H₂S levels, thereby underscoring the probe's immense potential as an effective tool for the diagnosis and prevention of Alzheimer's disease.