Nitric Oxide Linked to Parkinson's, Alzheimer's, and Huntington's

Researchers at Sanford-Burnham Medical Research Institute, La Jolla, CA, have discovered that the untimely death of brain cells that characterize Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease can be traced back, in some cases, to the untimely transfer of nitric oxide (NO)—not to be confused with nitrous oxide—from one protein to another.

“We and other researchers have shown that NO and related molecules can contribute to either nerve cell death or nerve cell survival. However, these new findings reveal that NO can actually jump from one protein to another in molecular pathways that lead to cellular suicide,” explained Stuart A. Lipton, MD, PhD, senior author, and director, Del E. Web Center for Neuroscience, Aging and Stem Cell Research, Sanford-Burnham. “Now that we have this molecular clue to the cause of nerve cell death in Parkinson’s, Alzheimer’s, and Huntington’s diseases, we can figure out how to use it to better diagnose and treat these diseases.”

The researchers specifically found that NO-like molecules a transferred from caspases—which normally initiate cell death—to XIAP, which normally inhibits cell death. With cells programmed to self-destruct when NO is attached to XIAP or not attached to caspases, the result of the transfer is a double whammy that is more common in the brains of those with neurodegenerative diseases than in the brains of those who are “normal.”

Taking their findings to the next level, Lipton’s team is “currently analyzing cerebrospinal fluid and brain tissue from Parkinson’s, Alzheimer’s and other patients to determine if we can use the NO-tagged proteins as biomarkers for the disease,” he said.

The results were published online today in Molecular Cell.

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