Endoplasmic Reticulum-Targeted Two-Photon Fluorescent Probe for the Detection of Nitroxyl in a Parkinson’s Disease Model

Abstract

Nitroxyl (HNO) and endoplasmic reticulum (ER) stress are considered to play important effects in the administration of many pathological processes of Parkinson’s disease (PD). However, the intricate relationship between the neurotoxicity of HNO and ER stress in the processes of PD is still unknown. To completely comprehend the pathogenic activity of HNO during ER stress and achieve early diagnosis of PD, developing sensitive tools for HNO sensing in vivo is essential. In this work, a two-photon fluorescent probe (KD-HNO) was developed with highly selective and sensitive (7.93 nM) response for HNO in vitro. Then, utilizing KD-HNO, we found that HNO levels were distinctly increased in tunicamycin-stimulated PC12 cells, which are characterized by ER stress and PD features. Most importantly, we detected a considerable increase in HNO levels in the brains of PD-model mice, indicating a positive correlation between PD and HNO levels for the first time. Collectively, these findings revealed that KD-HNO is an excellent tool not only for understanding the biological effects of HNO in pathological processes of PD but also for early PD diagnosis.

Promising Molecular Architectures for Two-Photon Probes in the Diagnosis of α-Synuclein Aggregates

“…Molecules 2024, 29, x FOR PEER REVIEW 2 of 19 TPE probes have been developed for detecting β-amyloid plaques and tau aggregates [6][7][8][9][10][11][12][13]. However, to the best of our knowledge, there remains a lack of dedicated probes for α-synuclein (α-syn) aggregates.…”

“…Optical imaging-based approaches based on two-photon excitation (TPE), on the other hand, can allow for both high spatial and temporal resolution. To date, numerous TPE probes have been developed for detecting β-amyloid plaques and tau aggregates [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. However, to the best of our knowledge, there remains a lack of dedicated probes for α-synuclein (α-syn) aggregates.…”

“…Optical imaging-based approaches based on two-photon excitation (TPE), on the other hand, can allow for both high spatial and temporal resolution. To date, numerous TPE probes have been developed for detecting β-amyloid plaques and tau aggregates [6][7][8][9][10][11][12][13]. However, to…”

Ratiometric photoacoustic imaging of endogenous HNOin vivofor assessing prodrug release and liver injury

“…S12, ESI†). 14 The results indicated that probe NF could be used as an efficient imaging tool for HNO detection in vivo . Above all, ratiometric probe NF can selectively and rapidly detect HNO in vitro and in complex living systems.…”

An activatable fluorescent-photoacoustic dual-modal probe for highly sensitive imaging of nitroxyl in vivo

“…However, the specific physiological mechanisms of nitroxide are still not well known due to the lack of effective detection methods. 11,12 Accurately detecting the production of endogenous HNO could greatly promote the research of HNO-associated diseases. Hence, developing novel techniques to effectively measure HNO in vivo is of great significance.…”