Aktywowana peroksynitrytem poprzeczka walpropinianu do monitorowania stresu oksydacyjnego i zmniejszania napadów padaczki w modelu epilepsji
Peroxynitrite-Activated Valproic Acid Precursor for Monitoring Oxidative Stress and Reducing Epileptic Seizures in an Epilepsy Model
W skrócie
Naukowcy opracowali specjalne lekarstwo, które aktywuje się w obecności peroksynitranu - szkodliwej substancji związanej z padaczką. Kiedy lekarstwo się aktywuje, uwalnia walpropinian (lek przeciwpadaczkowy) i wysyła fluorescencyjny sygnał, dzięki czemu lekarze mogą obserwować szkodliwe substancje w mózgu. W badaniach na myszach lek zmniejszył częstość napadów padaczki i wydłużył czas między napadami, otwierając nowe możliwości diagnozowania i leczenia padaczki.
Oryginalny abstract (angielski)
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, which poses a significant threat to human health. Increasing evidence indicates that the pathological mechanism of epilepsy is closely related to the presence of peroxynitrite (ONOO). To address this issue, we have developed a dual-molecule release precursor, , with different functional components, which consists of a responsive group, a reporter segment, and a drug molecule, for monitoring peroxynitrite. Based on assays, exhibits several advantages, including high specificity, a rapid response time (120 s), and a dual release function, and is not affected by other reactive oxygen species. When this precursor is activated by peroxynitrite, valproic acid (VPA) is released, which is a broad-spectrum antiepileptic drug that can reduce seizure occurrences; a near-infrared (NIR) reporter unit is formed synchronously using , and we successfully tracked the fluctuations of endogenous and exogenous ONOO in SH-SY5Y cells and achieved significant spatiotemporal resolution. Moreover, can clearly display the changes of endogenous ONOO in SH-SY5Y cells. Crucially, helps to perform fluorescence imaging of the ONOO concentration in epilepsy models, while also reducing the seizure levels in mice and shortening their seizure latency, for the first time. These findings indicate that provides a promising tool for the diagnosis and treatment of epilepsy by imaging the fluctuations of ONOO, and offers a reliable method for studying the treatment of epilepsy.