Alzheimer's disease is the most common neurodegenerative disorder. One of the factors that promotes neurodegeneration is the accumulation of senile plaques formed by Aβ peptide. In this paper, it was analyzed that if oxidative stress is cause or consequence of amyloid cascade and the role of antioxidant defense system in this process, using S. cerevisiae (with a multicopy plasmid containing the Aβ1-42 sequence) as experimental model. Cells grown on glycerol were more tolerant than when grown on glucose, strengthening the role of the antioxidant defense system against Aβ accumulation. Antioxidant defense deficiency did not change the pattern of amyloid aggregation. On the other hand, the presence of Aβ increased the level of intracellular oxidation and induced the activity of catalase, superoxide dismutase, and aconitase. Peroxissomal catalase deficient cells (Δcta1), were more sensitive to Aβ toxicity than the wild type strain, while mitochondrial superoxide dismutase (Sod2) deficient cells displayed the highest frequency of petites. Besides, Aβ alters the oxygen consumption and the activity of complex III and IV. Taken together, our results point out that the Aβ toxicity mechanism involves an oxidative stress induction by increasing ROS production into the mitochondria, where Cta1 and Sod2 play a crucial role in the regulation of the redox balance. J. Cell. Biochem. 118: 1442-1452, 2017. © 2016 Wiley Periodicals, Inc.

• PMID: 27883213
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Journal Article

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França MB, Lima KC, Eleutherio EC

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