Investigation of the effect of auranofin, cisplatin, and gliptins on the neurolysin catalytic activity

Abstract

Neurolysin is a zinc metallopeptidase belonging to the M3 family of endopeptidases. It can be found in different cellular components, such as the cytosol, mitochondria, and plasma membrane. It plays a crucial role in breaking down neurotoxic and cerebrotoxic neuropeptides. Neurolysin plays an important role in stroke and some cancer types. Enhancing neurolysin is deemed to be a promising therapeutic approach for stroke, while inhibiting neurolysin is believed to be a potential therapeutic approach for specific types of cancer.This study aimed to evaluate the effects of various approved drugs, such as auranofin, cisplatin, alogliptin, linagliptin, sitagliptin, and vildagliptin, on the activity of neurolysin and related enzymes. The majority of experiments were carried out using fluorometric enzyme assays and recombinant proteins. Our results show that auranofin selectively inhibits neurolysin at nanomolar concentrations, potentially offering a previously unrecognized mechanism of action for this drug.