Frontiers in Neurology (Sep 2017)

Peripheral Oxidative Stress Biomarkers in Spinocerebellar Ataxia Type 3/Machado–Joseph Disease

  • Adriano M. de Assis,
  • Adriano M. de Assis,
  • Jonas Alex Morales Saute,
  • Jonas Alex Morales Saute,
  • Jonas Alex Morales Saute,
  • Jonas Alex Morales Saute,
  • Jonas Alex Morales Saute,
  • Aline Longoni,
  • Clarissa Branco Haas,
  • Vitor Rocco Torrez,
  • Andressa Wigner Brochier,
  • Gabriele Nunes Souza,
  • Gabriel Vasata Furtado,
  • Gabriel Vasata Furtado,
  • Tailise Conte Gheno,
  • Tailise Conte Gheno,
  • Aline Russo,
  • Thais Lampert Monte,
  • Thais Lampert Monte,
  • Raphael Machado Castilhos,
  • Artur Schumacher-Schuh,
  • Artur Schumacher-Schuh,
  • Rui D’Avila,
  • Karina Carvalho Donis,
  • Carlos Roberto de Mello Rieder,
  • Carlos Roberto de Mello Rieder,
  • Carlos Roberto de Mello Rieder,
  • Diogo Onofre Souza,
  • Diogo Onofre Souza,
  • Suzi Camey,
  • Suzi Camey,
  • Vanessa Bielefeldt Leotti,
  • Vanessa Bielefeldt Leotti,
  • Laura Bannach Jardim,
  • Laura Bannach Jardim,
  • Laura Bannach Jardim,
  • Laura Bannach Jardim,
  • Laura Bannach Jardim,
  • Luis Valmor Portela,
  • Luis Valmor Portela

DOI
https://doi.org/10.3389/fneur.2017.00485
Journal volume & issue
Vol. 8

Abstract

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ObjectivesSpinocerebellar 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.MethodsMolecularly 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.ResultsFifty-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).ConclusionEarly/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.

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