Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-β42: importance of lipid homeostasis

摘要: Amyloid-β (Aβ)-containing plaques are a major neuropathological feature of Al- zheimer's disease (AD). The two isoforms Aβ peptide associated with AD Aβ40 and Aβ42, which the latter is highly prone to aggregation. Increased presence aggre- gation intracellular Aβ42 peptides an early event in progression. Improved under- standing cellular processes affecting aggregation may have implications for develop- ment therapeutic strategies. fused green fluorescent protein (A β42-GFP) was expressed ∼4600 mutants Saccharomyces cerevisiae genome-wide deletion library identify proteins by assessing fluorescence A β42-GFP. This screening identified 110 exhibiting intense β42- GFP-associated fluorescence. Four were overrepresented data set, including phospholipid homeostasis. Disruption phosphatidylcholine, phosphati- dylserine, and/or phosphatidylethanolamine metabolism had effect on localization. Confocal microscopy indicated that Aβ42-GFP localiza- tion juxtaposed nucleus, most likely endoplasmic reticulum (ER)/ER membrane. These provide indication affect important understanding mechanisms