Redox Imbalance Associates with Clinical Worsening in Spinocerebellar Ataxia Type 2

Background. Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease presenting with redox imbalance. However, the nature and implications of redox imbalance in SCA2 physiopathology have not been fully understood. Objective. The objective of this study is to assess the redox imbalance and its association with disease severity in SCA2 mutation carriers. Methods. A case-control study was conducted involving molecularly confirmed SCA2 patients, presymptomatic individuals, and healthy controls. Several antioxidant parameters were assessed, including serum thiol concentration and the superoxide dismutase, catalase, and glutathione S-transferase enzymatic activities. Also, several prooxidant parameters were evaluated, including thiobarbituric acid-reactive species and protein carbonyl concentrations. Damage, protective, and OXY scores were computed. Clinical correlates were established. Results. Significant differences were found between comparison groups for redox markers, including protein carbonyl concentration (F=3.30; p=0.041), glutathione S-transferase activity (F=4.88; p=0.009), and damage (F=3.20; p=0.045), protection (F=12.75; p<0.001), and OXY (F=7.29; p=0.001) scores. Protein carbonyl concentration was positively correlated with CAG repeat length (r=0.27; p=0.022), while both protein carbonyl concentration (r=−0.27; p=0.018) and OXY score (r=−0.25; p=0.013) were inversely correlated to the disease duration. Increasing levels of antioxidants and decreasing levels of prooxidant parameters were associated with clinical worsening. Conclusions. There is a disruption of redox balance in SCA2 mutation carriers which depends on the disease stage. Besides, redox changes associate with markers of disease severity, suggesting a link between disruption of redox balance and SCA2 physiopathology