Peptidase neurolysin is an endogenous cerebroprotective mechanism in acute neurodegenerative disorders

Stroke and traumatic brain injury (TBI) are significant clinical problems characterized by high rate of mortality and long-lasting disabilities, and an unmet need for new treatments. Current experimental stroke and TBI research are evolving to focus more on understanding the brain's self-protective mechanisms to meet the critical need of developing new therapies for these disorders. In this hypothesis-based manuscript, I provide several lines of evidence that peptidase neurolysin (Nln) is one of the brain's potent, self-protective mechanisms promoting preservation and recovery of the brain after acute injury. Based on published experimental observations and ongoing studies in our laboratory, I posit that Nln is a compensatory and cerebroprotective mechanism in the post-stroke/TBI brain that functions to process a diverse group of extracellular neuropeptides and by that to reduce excitotoxicity, oxidative stress, edema formation, blood brain barrier hyper-permeability, and neuroinflammation. If this hypothesis is correct, Nln could potentially serve as a single therapeutic target to modulate the function of multiple targets, the involved neuropeptide systems, critically involved in various mechanisms of brain injury and cerebroprotection/restoration. Such multi-pathway target would be highly desired for pharmacotherapy of stroke and TBI, because targeting one pathophysiological pathway has proven to be ineffective for such complex disorders.