The redox modulatory effects of SP/NK1R system: Implications for oxidative stress-associated disorders.

Oxidative stress which refers to redox imbalance with increased generation of reactive oxygen species (ROS) has been associated with the pathophysiology of diverse disease conditions. Recently, a close, yet not fully understood, relation between oxidative stress and neuropeptides, in particular, substance P (SP), has been reported in certain conditions. SP has been shown to affect the cellular redox environment through activation of neurokinin-1receptor (NK1R). It seems that SP/NK1R system and oxidative stress can act either synergistically or antagonistically in a context-dependent manner, thereby, influencing the pathology of various clinical disorders either destructively or protectively. Importantly, the interactions between oxidative stress and SP/NK1R system can be pharmacologically targeted. Therefore, a better understanding of the redox modulatory properties of SP/NK1R signaling will pave the way for identifying new therapeutic possibilities for attenuating oxidative stress-mediated damage. Towards this end, we performed a comprehensive search through PubMed/Medline and Scopus databases and discussed all related existing literature regarding the interplay between oxidative stress and SP/NK1R system as well as their implication in various clinical disorders, to provide a clear view and hence better management of oxidative damage.