(From Medical News Today). Scientists are increasing their understanding of the biochemical mechanisms by which oxidative stress causes neurodegeneration: researchers "have discovered a mechanistic link between cellular stress caused by free radicals and accumulation of misfolded proteins that lead to nerve cell injury and death in neurodegenerative disorders such as Alzheimer's and Parkinson's Disease. That link is Protein Disulphide Isomerase (PDI) ... The accumulation of misfolded proteins is a common pathogenic mechanism in many diseases, including neurodegenerative disorders. In normal circumstances, PDI levels increase in response to accumulation of misfolded proteins due to cellular stress. ... molecules related to the free radical NO, which is present in elevated levels in neurodegenerative diseases, [alters PDI's structure to block] its normal neuroprotective function, which ultimately leads to nerve cell injury and even death."