| Nitric oxide (NO) is a free radical that is released and utilized by the Central Nervous System (CNS) for neurotransmission and differentiation. NO is toxic when released at a high flux rate. During CNS injury and neurodegenerative diseases, such as Multiple Sclerosis, Alzheimer's disease, or Amyotrophic Lateral Sclerosis, high levels of NO is released, forming peroxynitrite and subsequently 3-nitrotyrosine, which leads to cell death. The heme oxygenase-1 enzyme (HO-1) breaks down heme and produces the metabolites, carbon monoxide (CO), iron, and biliverdin. Studies have shown that HO-1 protects cells from oxidative stress. Motor neuron cells, NSC-34, were pre-treated with CO, iron and bilirubin and then challenged with NO. Cells pretreated with CO showed greater resistance to NO challenge than cells receiving NO challenge alone. CO abrogates peroxynitrite-mediated NO toxicity in motor neurons and may be a new therapeutic target for mitigation of CNS disease and injury. |
