Elevated Nitric Oxide Levels Contribute to Neuron Damage

Elevated levels of nitric oxide (NO) mediate the activation of cell death signaling cascades characteristic of many neurodegenerative disorders.

Physiological levels of NO usually protect neurons from damage by inhibiting caspase activity. However, elevated NO levels have now been linked to the type of neuron damage and death that characterizes neurodegenerative disorders such as Alzheimer's, Huntington's, and Parkinson's diseases.

Investigators at the Sanford-Burnham Medical Research Institute (La Jolla, CA, USA) examined the relationship between NO and the caspase inhibitor X-linked inhibitor of apoptosis (XIAP). XIAP is a member of a family of inhibitors that help preserve neurons by blocking the activity of factors that trigger the cell death (apoptosis) pathway.

They reported in the July 30, 2010, issue of the journal Molecular Cell that high levels of NO induced the formation of a modified, S-nitrosylated form of XIAP called SNO-XIAP. The addition of NO to the XIAP molecule resulted in loss of antiapoptotic activity and in an increase in cell damage and death. Significant SNO-XIAP formation was found in the brains of patients with Alzheimer's, Parkinson's, and Huntington's diseases.

The investigators are seeking a mechanism to prevent the formation of SNO-XIAP, which should reduce or repair the damage to neurons seen in the neurodegenerative diseases.

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Sanford-Burnham Medical Research Institute