Yeast as a tool to unveil the cellular and molecular mechanisms underlying neurodegeneration in FENIB disease

The yeast Saccharomyces cerevisiae has contributed significantly to the understanding of the basic biology of a variety of eukaryotic cellular processes and it is an established model organism for the analysis of evolutionarily conserved cellular pathways relevant for protein degradation, including human neurotoxic proteins, aging and cell death [1]. FENIB (Familial encephalopathy with neuroserpin inclusion bodies) is a rare neurodegenerative disease with autosomal dominant inheritance caused by different mutations in neuroserpin gene (NS1) that promote polymerization and intracellular deposition of this protein. The severity of the phenotype depends on the specific mutation. Symptoms are dementia, epilepsy and also rapid and involuntary movement of the muscles. Despite several studies conducted so far on different cell models there is not a resolving cure for this disease [2]. We aim to use S. cerevisiae as a new cellular model useful for analyzing the characteristic aspects of FENIB disease, with the final purpose to identify the molecular mechanisms of cytotoxicity and possible new targets for therapeutic intervention. In this context, humanized yeast models could be a powerful tool for accelerating and facilitating the identification of cellular players, bio-molecular pathways involved in FENIB beginning and development, highlighting the value of using yeast as a model organism for the study of neurodegenerative diseases. References [1] Fruhmann, G et al.,. (2017) Yeast buddies helping to unravel the complexity of neurodegenerative disorders. Mech Ageing Dev. Jan;161(Pt B):288-305. [2] Guadagno, NA et al., (2017) Neuroserpin polymers cause oxidative stress in a neuronal model of the dementia FENIB. Neurobiology of Disease, 103:32-44