Neurodegeneration: Impact of S-nitrosylated Parkin, DJ-1 and PINK1 on Parkinson's disease.

Abstract Parkinson's disease (PD) is one of the fastest-growing neurodegenerative disorders in the world. PD is the most common movement disorder and the second most common neurodegenerative disorder after Alzheimer's disease. The incidence of idiopathic PD increases with age, however, some forms of recessively-inherited familial PD are responsible for cases with earlier onset and are associated with mutations in genes encoding three vital PD-related proteins: Parkin, DJ-1, and PINK1. All three of these proteins have been implicated in maintaining the proper mitochondrial function, which may be particularly important for neuronal health. Aberrant post-translational modifications of these proteins may disrupt their cellular functions and contribute to the onset of idiopathic PD as well. Some post-translational modifictions can be caused by the overabundance of harmful reactive oxygen/nitrogen species (ROS/RNS) inside the cell. Oxidative and nitrosative stress can exacerbate the intensity and progression of the disease. Unlike oxidative modifications of these proteins, the covalent modification of these three proteins by NO under nitrosative stress, i.e. S-nitrosylation of Parkin, DJ-1; and PINK1, is less studied. Here, we review the available literature on S-nitrosylation of these three proteins, their importance in the onset of PD, and few important denitrosylating systems in cells.