Cellular and Molecular Neurobiology

, Volume 34, Issue 2, pp 157–165 | Cite as

Neurological Damage in MSUD: The Role of Oxidative Stress

  • Angela Sitta
  • Graziela S. Ribas
  • Caroline P. Mescka
  • Alethéa G. Barschak
  • Moacir Wajner
  • Carmen R. VargasEmail author
Review Paper


Maple syrup urine disease (MSUD) is a metabolic disease caused by a deficiency in the branched-chain α-keto acid dehydrogenase complex, leading to the accumulation of branched-chain keto acids and their corresponding branched-chain amino acids (BCAA) in patients. Treatment involves protein-restricted diet and the supplementation with a specific formula containing essential amino acids (except BCAA) and micronutrients, in order to avoid the appearance of neurological symptoms. Although the accumulation of toxic metabolites is associated to appearance of symptoms, the mechanisms underlying the brain damage in MSUD remain unclear, and new evidence has emerged indicating that oxidative stress contributes to this damage. In this context, this review addresses some of the recent findings obtained from cells lines, animal studies, and from patients indicating that oxidative stress is an important determinant of the pathophysiology of MSUD. Recent works have shown that the metabolites accumulated in the disease induce morphological alterations in C6 glioma cells through nitrogen reactive species generation. In addition, several works demonstrated that the levels of important antioxidants decrease in animal models and also in MSUD patients (what have been attributed to protein-restricted diets). Also, markers of lipid, protein, and DNA oxidative damage have been reported in MSUD, probably secondary to the high production of free radicals. Considering these findings, it is well-established that oxidative stress contributes to brain damage in MSUD, and this review offers new perspectives for the prevention of the neurological damage in MSUD, which may include the use of appropriate antioxidants as a novel adjuvant therapy for patients.


MSUD Oxidative stress Free radicals Antioxidants 


Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Angela Sitta
    • 1
  • Graziela S. Ribas
    • 1
  • Caroline P. Mescka
    • 2
  • Alethéa G. Barschak
    • 3
  • Moacir Wajner
    • 1
    • 2
  • Carmen R. Vargas
    • 1
    • 2
    • 4
    Email author
  1. 1.Serviço de Genética MédicaHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Ciências Biológicas: BioquímicaUFRGSPorto AlegreBrazil
  3. 3.Departamento de Ciências Básicas da SaúdeUFCSPAPorto AlegreBrazil
  4. 4.Programa de Pós-Graduação em Ciências FarmacêuticasUFRGSPorto AlegreBrazil

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