Free radicals and neural diseases

A new study offers the first evidence that explains the link between cellular stress caused by free radicals and the protein misfolding that is associated with several neurodegenerative diseases, according to its authors. Patients with these diseases, which include Parkinson's and Alzheimer's, produce excess amounts of nitric oxide free radical. Stuart A. Lipton of Burnham Institute for Medical Research in La Jolla, Calif., and colleagues report that the NO group S-nitrosylates critical cysteine residues in protein-disulfide isomerase (PDI). The reaction alters PDI's structure and interferes with its role in fixing misfolded proteins in nerve cells (Nature 2006, 441, 513). The misfolded proteins then accumulate and damage or kill off the affected neurons. The researchers suggest that the elevated levels of S-nitrosylated PDI in Alzheimer's and Parkinson's patients could serve as a biomarker for development of these diseases. Reducing levels of this damaged protein could have therapeutic benefit, they add.