Mitochondrial Dysfunctional and Oxidative Stress: Biochemical Insight Into Neurodegenerative Disorder

Though these are important indicators of neurodegeneration, molecular mechanisms that relate mitochondrial failure to oxidative stress in major diseases are not well understood. Objective: This study aims to investigate antioxidant defence mechanisms, biomarkers of oxidative stress, and key indices of mitochondrial function in the context of Parkinson’s disease (PD) and Alzheimer’s disease (AD). It further seeks to evaluate their diagnostic utility and interrelationships. Methods: The number of participants was 210 (70 AD, 70 PD, and 70 healthy controls). The mitochondrial membrane potential ( Δ ψm), complex I and IV activity and copy number of mitochondrial DNA (mtDNA) of the plasma and peripheral blood mononuclear cells were measured. The oxidative stress was measured using reactive oxygen species (ROS), malondialdehyde (MDA), 8-hydroxy-23-deoxyguanosine (8-OHdG) and F2-isoprostanes. The glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were used in the measurement of antioxidant defences. Correlations and receiver operating characteristics (ROC) analyses were conducted and group differences were compared with ANCOVA. Results: The decreases in the mitochondrial DNA copy numbers, complex I/IV activity and 2.9-Hydrogen peroxidem of both AD and PD patients were significant compared with the controls (all p<0.001). The SOD activity of the patients was reduced with higher oxidative stress (ROS, MDA and 8-OHdG) and no patterns could be observed in catalase and GPx. On correlation, the mitochondrial indices are negatively correlated to oxidative indicators but positively correlated to cognitive performance (MMSE). The ROC analysis has calculated the area under the curve (AUC) and it was 0.634, which implies that these biomarkers have moderate discriminating power. Conclusions: Oxidative stress and mitochondrial dysfunction are mutually related in AD and PD, and this supports the hypothesis of the vicious loop of neurodegeneration. Single markers even though not very diagnostic, may improve diagnostic and therapeutic intervention in combination with multimodal panels, with new CSF-plasma biomarkers and bioinformatics-related omics.