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Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity

The Cerebellum volume 17, pages 601–609 (2018)Cite this article

Abstract

Spinocerebellar ataxia type 7 is a neurodegenerative inherited disease caused by a CAG expansion in the coding region of the ATXN7 gene, which results in the synthesis of polyglutamine-containing ataxin-7. Expression of mutant ataxin-7 disturbs different cell processes, including transcriptional regulation, protein conformation and clearance, autophagy, and glutamate transport; however, mechanisms underlying neurodegeneration in SCA7 are still unknown. Implication of oxidative stress in the pathogenesis of various neurodegenerative diseases, including polyglutamine disorders, has recently emerged. We perform a cross-sectional study to determine for the first time pheripheral levels of different oxidative stress markers in 29 SCA7 patients and 28 age- and sex-matched healthy subjects. Patients with SCA7 exhibit oxidative damage to lipids (high levels of lipid hydroperoxides and malondialdehyde) and proteins (elevated levels of advanced oxidation protein products and protein carbonyls). Furthermore, SCA7 patients showed enhanced activity of various anti-oxidant enzymes (glutathione reductase, glutathione peroxidase, and paraoxonase) as well as increased total anti-oxidant capacity, which suggest that activation of the antioxidant defense system might occur to counteract oxidant damage. Strikingly, we found positive correlation between some altered oxidative stress markers and disease severity, as determined by different clinical scales, with early-onset patients showing a more severe disturbance of the redox system than adult-onset patients. In summay, our results suggest that oxidative stress might contribute to SCA7 pathogenesis. Furthermore, oxidative stress biomarkers that were found relevant to SCA7 in this study could be useful to follow disease progression and monitor therapeutic intervention.

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Acknowledgments

This work was supported by SEP-CONACyT (grant number CB-2015-01-258043) to JJ-M. This study is dedicated to the patients and the members of SCA7-affected families. We also thank Yessica Tapia-Guerrero, Joan Jano-Ito, and César Cerecedo for technical assistance.

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Affiliations

  1. Department of Immunobiochemistry, National Perinatology Institute (INPer), Mexico City, Mexico

    Y. Torres-Ramos, A. Montoya-Estrada & G. León-Reyes

  2. Department of Genetics and Molecular Biology, Center of Research and Advanced Studies (CINVESTAV-IPN), Mexico City, Mexico

    B. Cisneros

  3. Rehabilitation and Social Inclusion Center of Veracruz (CRIS-DIF), Xalapa, Veracruz, Mexico

    K. Tercero-Pérez

  4. Laboratory of Genomic Medicine, Department of Genetics, National Rehabilitation Institute-Luis Guillermo Ibarra Ibarra (INR-LGII), Mexico City, Mexico

    N. Leyva-García, Oscar Hernández-Hernández & Jonathan J. Magaña

Authors
  1. Y. Torres-Ramos
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  2. A. Montoya-Estrada
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  3. B. Cisneros
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  4. K. Tercero-Pérez
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  5. G. León-Reyes
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  6. N. Leyva-García
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  7. Oscar Hernández-Hernández
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  8. Jonathan J. Magaña
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Corresponding authors

Correspondence to Oscar Hernández-Hernández or Jonathan J. Magaña.

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An informed consent form was signed by all subjects prior to examination and the research protocol was approved by the National Rehabilitation Institute (INR, Mexico City) Research and Ethical Committee.

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The authors declare that they have no conflicts of interest.

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Torres-Ramos, Y., Montoya-Estrada, A., Cisneros, B. et al. Oxidative Stress in Spinocerebellar Ataxia Type 7 Is Associated with Disease Severity. Cerebellum 17, 601–609 (2018). https://doi.org/10.1007/s12311-018-0947-0

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  • DOI: https://doi.org/10.1007/s12311-018-0947-0

Keywords

  • Spinocerebellar ataxia type 7
  • Oxidative stress
  • Blood biomarkers
  • Lipid oxidation
  • Protein oxidation
  • Antioxidant defense