近日，华东师范大学Qi-Wei Zhang团队研究了线粒体特异性蛋氨酸亚砜还原酶活性的双通道磷光比率测定和磷光寿命成像。相关论文发表在2025年5月14日出版的《美国化学会志》上。

蛋氨酸亚砜还原酶（Msrs）对于维持神经系统的氧化还原稳态至关重要，阿尔茨海默病（AD）与失调有关。传统的基于荧光的Msrs活性传感检测受到背景干扰、灵敏度有限和定量不足的阻碍。研究组介绍了一种新型超分子探针，在微秒时间尺度上在水介质中表现出氧化还原响应的双通道室温磷光（RTP）。

在被Msrs还原后，探针从氧化状态转变为还原状态，表现为红移磷光发射和微秒范围内的寿命延长，这使得能够通过磷光比率测定和磷光寿命成像（PLIM）精确定量线粒体靶向Msrs活性。该探针的实用性在可视化小鼠大脑中的神经元Msrs活性和分布方面得到了证明，这揭示了AD模型中Msrs活性的显著下调，突显了该探针在阐明神经退行性疾病的氧化还原相关病理机制方面的潜力。 

附：英文原文

Title: Dual-Channel Phosphorescence Ratiometry and Phosphorescence Lifetime Imaging of Mitochondria-Specific Methionine Sulfoxide Reductase Activity

Author: Xuewei Wang, Chen Chen, Yang Tian, Qi-Wei Zhang

Issue&Volume: May 14, 2025

Abstract: Methionine sulfoxide reductases (Msrs) are essential for preserving redox homeostasis in the nervous system, with dysregulation implicated in Alzheimer’s disease (AD). Conventional fluorescence-based assays for Msrs activity sensing are hampered by background interference, limited sensitivity, and inadequate quantification. This work introduces a novel supramolecular probe exhibiting redox-responsive dual-channel room-temperature phosphorescence (RTP) in aqueous media on a microsecond time scale. Upon reduction by Msrs, the probe transitions from its oxidized to reduced state, manifested by a red-shifted phosphorescence emission and extended lifetime in the microsecond range, which enables precise quantification of mitochondria-targeted Msrs activity via phosphorescence ratiometry and phosphorescence lifetime imaging (PLIM). The probe’s utility is demonstrated in visualizing neuronal Msrs activity and distribution within the mouse brain, which reveals a marked downregulation of Msrs activity in an AD model, highlighting the probe’s potential in elucidating redox-related pathological mechanisms underlying neurodegenerative disorders.

DOI: 10.1021/jacs.5c03235

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.5c03235