Neurotoxic Actions and Mechanisms of Nitric Oxide

Publisher Summary Nitric oxide (NO) has revolutionized the perception of neurotransmission and neuronal signaling. It is emerging as a key regulator of numerous physiological responses. However, excessive generation of NO can mediate neuronal damage in a variety of neurologic diseases. Understanding the pathways through which NO causes neuronal cell death is key in the development of more effective therapies. This chapter reviews the current knowledge on the mechanisms of NO-mediated neurotoxicity. NO damages neurons in the reaction with superoxide anion to generate peroxynitrite. Peroxynitrite is a potent cellular toxin and is capable of altering proteins, lipids, and DNA. NO may interact directly with a large number of proteins and cause subsequent alteration of their function. NO-induced cell death is characterized by typical features of both necrosis and/or apoptosis. NO plays a role as a neuronal-cell-death mediator in a variety of disorders of the nervous system. This chapter discusses the involvement of NO in excitoxicity, stroke, ischemic reconditioning, and Parkinson's disease.