Yeast as a Model to Find New Drugs and Drug Targets for -Dependent Neurodegenerative Diseases.

Mutations in human genes result in rare neurological diseases, including chorea-acanthocytosis. The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one gene is present.

Partial Inhibition of Calcineurin Activity by Rcn2 as a Potential Remedy for Vps13 Deficiency.

Regulation of calcineurin, a Ca/calmodulin-regulated phosphatase, is important for the nervous system, and its abnormal activity is associated with various pathologies, including neurodegenerative disorders. In yeast cells lacking the gene (Δ), a model of -linked neurological diseases, we recently demonstrated that calcineurin is activated, and its downregulation reduces the negative effects associated with mutation. Here, we show that overexpression of the gene, which encodes a negative regulator of calcineurin, is beneficial for cells.

Flavonoids as Potential Drugs for -Dependent Rare Neurodegenerative Diseases.

Several rare neurodegenerative diseases, including chorea acanthocytosis, are caused by mutations in the - genes. Only symptomatic treatments for these diseases are available. contains a unique gene and the yeast Δ mutant has been proven as a suitable model for drug tests.

Yeast-model-based study identified myosin- and calcium-dependent calmodulin signalling as a potential target for drug intervention in chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a rare neurodegenerative disease associated with mutations in the human gene. The mechanism of ChAc pathogenesis is unclear. A simple yeast model was used to investigate the function of the single yeast VSP13 orthologue, Vps13.

Phosphatidylinositol-3-phosphate regulates response of cells to proteotoxic stress.

Human Nedd4 ubiquitin ligase, or its variants, inhibit yeast cell growth by disturbing the actin cytoskeleton organization and dynamics, and lead to an increase in levels of ubiquitinated proteins. In a screen for multicopy suppressors which rescue growth of yeast cells producing Nedd4 ligase with an inactive WW4 domain (Nedd4w4), we identified a fragment of ATG2 gene encoding part of the Atg2 core autophagy protein. Expression of the Atg2-C1 fragment (aa 1074-1447) improved growth, actin cytoskeleton organization, but did not significantly change the levels of ubiquitinated proteins in these cells.