Validation of Folate in a Convenient Yeast Assay Suited for Identification of Inhibitors of Alzheimer's Amyloid-β Aggregation

Genome-wide analysis ofSaccharomyces cerevisiaeidentifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-β42: importance of lipid homeostasis

“…S. cerevisiae has been exploited to study proteins implicated in neurodegenerative disorders including Huntington's disease (Willingham et al ., 2003; Giorgini et al ., 2005) and Parkinson's disease (Zhang et al ., 1994; Outeiro and Lindquist, 2003; Flower et al ., 2005). Yeast model systems have been exploited to study toxicity, aggregation, and localization of Aβ or as facile systems for identification of compounds influencing Aβ oligomerization (Zhang et al ., 1994, 1997; Komano et al ., 1998; Caine et al ., 2007; Macreadie et al ., 2008; Winderickx et al ., 2008; Treusch et al ., 2011). As indicated, protein tau has also been strongly correlated with several neuropathies, including AD.…”

Inhibition of Aβ42 oligomerization in yeast by a PICALM ortholog and certain FDA approved drugs

“…Among a handful of drugs that appear to inhibit Aβ 42 from forming toxic oligomers 62732414950515253 in pilot studies, several have reached clinical trials. Indeed, trials of PBT1 (clioquinol), a metal chelator, which modulates affinity for Cu 2+ and Zn 2+ and inhibits metal-induced Aβ 42 aggregation 65455 were dropped because of side effects 56.…”

“…Yeast has been used to screen for chemical compounds that reduce aggregation or oligomerization of the Aβ peptide by assaying for the activity of reporters fused to Aβ 2728. Previously, using a yeast Aβ 42 oligomerization model in which Aβ 42 was fused to the functional release factor (RF) domain of yeast translational termination factor, Sup35 29, we screened for anti-Aβ 42 oligomer compounds 28.…”

A plant cell-based system that predicts aβ42 misfolding: Potential as a drug discovery tool for Alzheimer's disease

“…Cell-based assays for screening of Aβ42 aggregation inhibitors have advantages over in vitro methods, as potential cytotoxicity of compounds is simultaneously assessed [15][16][17][18][19][20]. Toward this end, cell-based screens have been developed for Escherichia coli [17,18,21], yeasts [19,20], and mammalian cultured cells [16].…”

“…Toward this end, cell-based screens have been developed for Escherichia coli [17,18,21], yeasts [19,20], and mammalian cultured cells [16]. Prokaryotes and singlecelled eukaryotic organisms (i.e.…”