Neurolysin: From Initial Detection to Latest Advances

The mechanisms by which peptidergic signals are terminated have been the center of multiple studies leading to the discoveries of novel proteolytic activities. When studying the catabolic fate of neurotensin (NT) in brain and gastrointestinal tract, we detected a novel activity belonging to the metallopeptidases class and apparently distinct from previously known enzymes. Purification and cloning confirmed that this NT-degrading neutral metalloendopeptidase activity was indeed original. It was named endopeptidase 3.4.24.16 according to the IUBMB nomenclature and later, referred to as neurolysin. This review tells the history of neurolysin from its initial detection to its purification, cloning, design of specific inhibitors as well as in vitro and in vivo pharmacological studies aimed at delineating its role in the control of NT function. Finally, we discuss very recent advances suggesting a potential role of neurolysin in pathologies.