Scientists discover possible link between oxidative stress and non-hereditary degenerati...( tive stress? Aware of the connec...),Health

Aware of the connection between DJ-1 mutations and familial Parkinson's disease, Dr. Li and her collaborators examined the oxidation levels of the protein in sporadic cases. Their hypothesis that DJ-1 was the missing link proved to be correct: DJ-1 in patients who had Parkinson's disease showed signs of oxidative damage, including structural changes as the protein accumulated additional oxygen molecules (carbonylation and methonine oxidation).

These modifications to DJ-1 caused by the oxidative stress are irreversible and irreparable. Like familial Parkinson's disease, the structural changes to the DJ-1 protein in sporadic Parkinson's disease signal an abnormality, leading to the eventual degradation and loss of the protein. "The protein unfolds and cannot function normally," Dr. Li explains. "Not recognizing the unfamiliar shape, the protein is broken down by the cell. The end result is the same: you lose your protein. Any mutation or modification causing this protein to lose its function will then lead to neurodegeneration in Parkinson's disease."

Now that Dr. Li and her team are clear that a relationship between DJ-1 and neurodegeneration exists, they are preparing to extend their examination into the protein's role. Based on biochemical analysis, Dr. Li believes DJ-1 may serve as a protease, activating and deactivating a protein by cleaving the bonds that connect its amino acids. Dr. Li is also currently exploring the possibility that DJ-1 may serve as an antioxidant, and that when mutated or damaged, the protein cannot defend the cell.

Future information about the role of DJ-1 may enable the development of drugs to specifically target the protein, perhaps stopping or reversing Parkinson's disease or Alzheimer's disease, which also may be impacted by the oxidation of DJ-1. In the meantime, says Dr. Li, people looking to prevent neurological degeneration might do well by looking to the kitchen cabinet,
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
27-Apr-2006