Abstract
Parkinson's disease (PD) is caused by dopaminergic neuronal death in the substantia nigra, resulting in a reduced level of dopamine in the striatum. Oxidative stress and mitochondrial dysfunction are thought to be major causes of neurodegeneration in PD. Although genetic and environmental factors are thought to affect the onset of PD, precise mechanisms at the molecular level have not been elucidated. The DJ-1 gene is a causative gene for familial PD (park7) and also an oncogene. DJ-1 has various functions, including transcriptional regulation, antioxidative stress reaction, and chaperone, protease, and mitochondrial regulation, and its activity is regulated by its oxidative status, especially that of cysteine 106 (C106) of DJ-1. Excess oxidation of DJ-1, which renders DJ-1 inactive, has been observed in patients with sporadic PD and Alzheimer's disease, suggesting that DJ-1 also participates in the onset and pathogenesis of sporadic PD as well as familial PD. DJ-1 is also a stress sensor and its expression is increased upon various stresses, including oxidative stress. In this review, we describe functions of DJ-1 against oxidative stress and possible roles of DJ-1 in the pathogenesis of PD.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disease that occurs in approximately 1% of the population over the age of 65 years
When the sum of SH and SOH forms of cysteine 106 (C106) is more than 50% of total forms of C106, DJ-1 upregulates tyrosine hydroxylase (TH) and DOPA and L-DOPA carboxylase (DDC) activities, suggesting that the activity of DJ-1 toward TH and DDC is changed depending on the level of oxidative stress and that it is decreased with aging, which is one of the crucial factors for onset of PD (Figure 5)
Considering these findings, it is thought that localization of DJ-1 as a dimer in mitochondria is required for DJ-1 to play a role in antioxidative stress reaction and that DJ-1 localized in mitochondria as a monomer, such as M26I and L166P DJ-1, is, in contrast, harmful to cells
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease that occurs in approximately 1% of the population over the age of 65 years. Compared to parkin and Pink, other causative genes of familial PD with recessive inheritance, the number of mutations in the DJ-1 gene is small; numbers of mutations of the three genes are the order of parkin > Pink1 > DJ-1. This might be due to the position of DJ-1 during the course of onset of PD; DJ-1 may be placed upstream of Pink and parkin [1, 2].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
