Mitochondrial Complex I Inhibition in Parkinson's Disease: How Can Curcumin Protect Mitochondria?

Selective damage of mitochondrial complex I within the dopaminergic neurons of the substantia nigra is the central event during Parkinson disease. Peroxynitrite is one of the important free radicals probably mediating complex I damage. Peroxynitrite inhibits brain complex I mainly by 3-nitrotyrosine and nitrosothiol formation, but how these modifications alter the structure–function relation of complex I is unclear. Curcumin pretreatment protects brain mitochondria against peroxynitrite in vitro by direct detoxification and prevention of 3-nitrotyrosine formation and in vivo by elevation of total cellular glutathione levels. These results suggest a potential therapeutic role for curcumin against nitrosative stress in neurological disorders.