IMPACT OF THE ANTIOXIDANT EFFECT ON AΒ42-INDUCED CYTOTOXICITY IN SACCHAROMYCES CEREVISIAE

Abstract

Protein aggregation and increased reactive oxygen species (ROS) driving oxidative stress are hallmarks of neurodegenerative diseases. This study investigated the protective potential of the natural antioxidants ferulic acid (FA) and quercetin (Qc) against cytotoxicity induced by the Alzheimer's-associated β-amyloid peptide (Aβ42), using Saccharomyces cerevisiae as a eukaryotic model. Assays were performed using a wild-type strain (BY4741), an isogenic mutant deficient in the antioxidant transcription factor Yap1p (Δyap1), and a transformed strain expressing Aβ42. Experiments evaluated cell proliferation, mitochondrial membrane potential (ΔΨ), and intracellular oxidation levels. Results showed that both FA and Qc significantly reduced intracellular oxidation in WT and Δyap1 strains under H₂O₂-induced stress, as well as in the Aβ42-expressing strain. However, this antioxidant activity failed to rescue yeast metabolism from Aβ42 toxicity, which severely compromised cell proliferation rates and ΔΨ. These findings demonstrate that while FA and Qc effectively modulate the redox imbalance caused by Aβ42, their antioxidant effect does not directly translate into cellular protection against β-amyloid cytotoxicity. Consequently, although oxidative stress contributes to Aβ42-induced damage, mitigating this condition alone is insufficient to neutralize the fundamental pathological mechanisms that compromise eukaryotic cell survival.