Phycocyanin protects against Alpha-Synuclein toxicity in yeast

Abstract

Parkinson’s disease (PD) is an age-related neurodegenerative disorder associated with the misfolding and aggregation of alpha-synuclein (aSyn) in proteinaceous inclusions. These inclusions are common to a wider spectrum of disorders known as synucleinopathies. While the molecular bases of PD are still unclear, oxidative stress and impairment of protein quality-control systems play an important role, and are regarded as valuable targets for therapeutic interventions. We employed a yeast model of synucleinopathies to test the cytoprotective potential of phycocyanin, a biliprotein used as a nutritional supplement. We found that phycocyanin effectively protected against aSyn toxicity in yeast and, importantly, the mechanism of action involves the reduction of aSyn inclusions and superoxide levels, through the regulation of genes and enzymes involved in oxidative stress response, glutathione metabolism, and cellular protein quality-control systems. Overall, this study highlights the potential of phycocyanin as a nutraceutical in neurodegenerative diseases associated with proteotoxicity, such as synucleinopathies.