Parkinson’s disease (PD), with a prevalence of 2% of the population over the age of 65, is one of the most common neurodegenerative disorders and is characterized by resting tremor, rigidity, and bradykinesia. Current treatments are only symptomatic and do not alter the progression of the disease. PD patients, even under the best circumstances, typically deteriorate over time and experience considerable motor and cognitive disability in the years after diagnosis.
PD is characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the appearance of Lewy bodies in the remaining neurons. Although the primary cause of PD is still unknown, there has been growing evidence that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of PD. Dopaminergic neurons are particularly vulnerable to oxidative stress and oxidative stress-induced mitochondrial DNA mutations.
Oxidatively damaged mtDNA has been demonstrated to be significantly higher in PD postmortem brain samples than in age-matched controls. The oxidative mtDNA damage noted in
PD has been observed to be elevated in lymphocytes, cerebrospinal fluid, and serum. Urinary levels of 8-oxoG are also elevated in PD patients, correlating with the progression of the disease.
These studies all point to the critical role of oxidative stress and mtDNA damage in the pathogenesis of PD. Improving the functionality of OGG1 in PD patients may therefore positively impact the pathology of PD.