S-nitrosylation in Sporadic Parkinson's Disease and Cancer (Brain and Thyroid) Prevention

S-nitrosylation involves the covalent attachment of nitric oxide (NO) to a highly reactive sulfahydryl group of cysteine residues in proteins or peptides and emerges as a key figure in neurodegeneration and prevention of certain forms of cancer. Overproduction of NO appears to abrogate the proliferation of cancer cell lines by activation of p53 and in the same manner excessive apoptosis is linked to sporadic Parkinson's disease (PD), which is nonfamilial in nature. However, the mechanisms involved in p53 activation and induction of apoptosis by NO via Snitrosylation have not been fully elucidated. Parkin has been demonstrated to be neuroprotective by repressing p53 transcription under physiological conditions; in contrast, S-nitrosylation of parkin attenuates its interaction with p53 promoter and thus leading to p53 activation with a concomitant p53-mediated neuronal cell death. All together, S-nitrosylation of parkin as well as glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a molecular chaperone (protein-disulfide isomerase - PDI) and anti-apoptotic proteins (X-linked inhibitor of apoptosis - XIAP and peroxiredoxin 2 - Pdx2) is thought to be associated with sporadic PD. Conversely, NO donors (casmustine, auranofin and TNF-related apoptosis-inducing ligand - TRAIL) via S-nitrosylation could markedly enhance the efficacy in the prevention of brain and thyroid cancer cell lines. This review entails an overview in which Snitrosylation has been thought of as the good; the bad, and the ugly.