Thioketal-Based Electrochemical Sensor Reveals Biphasic Effects of l‑DOPA on Neuroinflammation

Abstract

Neuroinflammation is linked closely to neurodegenerative diseases, with reactive oxygen species (ROS) exacerbating neuronal damage. Traditional electrochemical sensors show promise in targeting cellular ROS to understand their role in neuropathogenesis and assess therapies. Nevertheless, these sensors face challenges in mitigating the ROS oxidation overpotential. We herein introduce an ROS oxidation-independent nucleic acid sensor for in situ ROS analysis and therapeutic assessment. The sensor comprises ionizable and thioketal (TK)-based lipids with methylene blue-tagged nucleic acids on a glass carbon electrode. ROS exposure triggers cleavage within the sensor’s thioketal moiety, detaching the nucleic acid from the electrode and yielding quantifiable results via square-wave voltammetry. Importantly, the sensor’s low potential window minimizes interference, ensuring precise ROS measurements with high selectivity. Using this sensor, we unveil levodopa’s dose-dependent biphasic effect on neuroinflammation: low doses alleviate oxidative stress, while high doses exacerbate it. The TK-based sensor offers a promising methodology for investigating neuroinflammation’s pathogenesis and screening potential treatments, advancing neurodegenerative disease research