Peripheral oxidative stress biomarkers in spinocerebellar ataxia type 3/Machado–Joseph disease

• Autor(a) principal: Assis, Adriano Martimbianco de
• Data de Publicação: 2017
• Outros Autores: Saute, Jonas Alex Morales, Santos, Aline Longoni dos, Haas, Clarissa Branco, Torrez, Vitor Rocco, Brochier, Andressa Wigner, Souza, Gabriele Nunes, Furtado, Gabriel Vasata, Gheno, Tailise Conte, Russo, Aline, Monte, Thais Lampert, Castilhos, Raphael Machado de, Schuh, Artur Francisco Schumacher, Davila, Rui, Donis, Karina Carvalho, Rieder, Carlos Roberto de Mello, Souza, Diogo Onofre Gomes de, Camey, Suzi Alves, Leotti, Vanessa Bielefeldt, Jardim, Laura Bannach, Portela, Luis Valmor Cruz
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFRGS
• Texto Completo: http://hdl.handle.net/10183/182527
• topic: Doença de Machado-Joseph; Estresse oxidativo; Espécies reativas de oxigênio; Estatística médica; Spinocerebellar ataxia type 3; Machado–Joseph disease; Oxidative stress; Reactive oxygen species; Polyglutamine disorders

Objectives: Spinocerebellar ataxia type 3/Machado–Joseph disease (SCA3/MJD) is a polyglutamine disorder with no current disease-modifying treatment. Conformational changes in mutant ataxin-3 trigger different pathogenic cascades, including reactive oxygen species (ROS) generation; however, the clinical relevance of oxidative stress elements as peripheral biomarkers of SCA3/MJD remains unknown. We aimed to evaluate ROS production and antioxidant defense capacity in symptomatic and presymptomatic SCA3/MJD individuals and correlate these markers with clinical and molecular data with the goal of assessing their properties as disease biomarkers. Methods: Molecularly confirmed SCA3/MJD carriers and controls were included in an exploratory case–control study. Serum ROS, measured by 2′,7′-dichlorofluorescein diacetate (DCFH-DA) as well as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) antioxidant enzyme activities, levels were assessed. Results: Fifty-eight early/moderate stage symptomatic SCA3/MJD, 12 presymptomatic SCA3/MJD, and 47 control individuals were assessed. The DCFH-DA levels in the symptomatic group were 152.82 nmol/mg of protein [95% confidence interval (CI), 82.57–223.08, p < 0.001] higher than in the control and 243.80 nmol/mg of protein (95% CI, 130.64–356.96, p < 0.001) higher than in the presymptomatic group. The SOD activity in the symptomatic group was 3 U/mg of protein (95% CI, 0.015–6.00, p = 0.048) lower than in the presymptomatic group. The GSH-Px activity in the symptomatic group was 13.96 U/mg of protein (95% CI, 5.90–22.03, p < 0.001) lower than in the control group and 20.52 U/mg of protein (95% CI, 6.79–34.24, p < 0.001) lower than in the presymptomatic group and was inversely correlated with the neurological examination score for spinocerebellar ataxias (R = −0.309, p = 0.049). Conclusion: Early/moderate stage SCA3/MJD patients presented a decreased antioxidant capacity and increased ROS generation. GSH-Px activity was the most promising oxidative stress disease biomarker in SCA3/MJD. Further longitudinal studies are necessary to identify both the roles of redox parameters in SCA3/MJD pathophysiology and as surrogate outcomes for clinical trials.