d-Arginine as a neuroprotective amino acid: promising outcomes for neurological diseases

In humans, as in other mammals, endogenous glucocorticoids (GCs) are essential for adapting to physiological life stress. They are also crucial for the healthy development of the fetus. However, when the physiological concentrations of GCs increase over a long period of time, the central nervous system (CNS) is predisposed to the development of psychiatric disorders and neurological diseases. Here, I discuss the strong influence of GCs on the nitric oxide (NO) pathway and the generation of reactive oxygen species (ROS). I also highlight supporting evidence for the neuroprotective actions of d-arginine (d-Arg) against neurotoxicity induced by high levels of GCs in the CNS. Given that d-Arg does not interfere with the immunosuppressive and anti-inflammatory effects of GCs, this might be a novel way of neutralizing the neurotoxic effects of GCs in the CNS without compromising their positive peripheral actions.