The nitric oxide pathways in the neurotoxicity from glutamate-induced apoptosis

Abstract

Glutamate is a key neurotransmitter in the central nervous system; however, excessive levels may produce neurotoxicity as well as the neurodegenerative diseases development. In the last time, multiples mechanisms underlying glutamate-induced neurotoxicity have been discussed. Likewise, apoptosis is a regulated process inherent to the normal cellular brain development and/or maintenance, nevertheless a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with neurodegeneration associated to an increase of the oxidative stress. Thus, a growing body of evidence suggests involvement of oxidative stress, inflammation and apoptosis in neurodegenerative diseases. To highlight, nitric oxide, an atypical neurotransmitter synthesized and released on demand by the post-synaptic neurons, it exerts many important implications for nerve cell survival and differentiation. Moreover, apoptosis induction or inhibition by nitric oxide may be explained by several mechanisms involving the expression/localization of the enzymatic precursors, bioavailability and/or possible protein interaction. Consequently, synaptogenesis, synapse elimination and neurotransmitter release, are nitric oxide-modulated. Finally, of particular interest to current knowledge, an emergent role of nitric oxide pathways has been discussed in the neurotoxicity from glutamate-induced apoptosis. These findings suggest that nitric oxide pathways modulation could prevents oxidative damage to neurons by apoptosis inhibition. This chapter aims at discussing the emergent aspects of nitric oxide-mediated signaling in the brain, and how they can be related to neurotoxicity as well as the neurodegenerative diseases development.