6/27/06(EurekAlert) - Parkinson's, Alzheimer's, Lou Gehrig's disease
and other brain disorders are among a growing list of maladies
attributed to oxidative stress, the cell damage caused during
metabolism when the oxygen in the body assumes ever more chemically
reactive forms.
But the precise connection between oxidation and neurodegenerative
diseases has eluded researchers. Now, a study by the Department of
Energy's Pacific Northwest National Laboratory and UCLA's David
Geffen School of Medicine reveals that damage is linked to a natural
byproduct of oxidation called nitration.

"We looked at a healthy brain and found nitration of proteins that
are implicated in neurodegenerative disease," said Colette
Sacksteder, PNNL scientist and lead author of the study, published
in the July issue of the journal Biochemistry (online Wed., June
28). PNNL scientist Wei-Jun Qian was co-lead author.

The results are from the most detailed proteomic analysis of a
mammalian brain to date – that is, a survey of nearly 8,000
different, detectable proteins in the mouse brain. The research
suggests that many neurodegenerative diseases leave a biochemical
calling card, or biomarker, that could be used to predict the
earliest stages of brain impairment. Many biomedical researchers
believe that detecting disease states before symptoms occur is the
key to reversing many as-yet-incurable diseases.

The biomarker is known as nitrotyrosine, made when an amino acid in
the brain, tyrosine, is in the presence of an oxidative-stress
molecule called peroxynitrate. The biomarker was found on 31 sites
along 29 different proteins, half of which had been previously
implicated in several of the neurodegenerative diseases.

"Our study certainly suggests that the sensitivity of certain
proteins to peroxynitrite is an early contributor to
neurodegeneration, but other factors may also be involved," said
Diana Bigelow, PNNL staff scientist and the paper's corresponding
author. "The next step, of explicitly looking at tissues with
neurodegenerative disease, will test this hypothesis."