Nair S~Perrone GG, 2014

Pubmed ID 24870034
Title Genome-wide analysis of Saccharomyces cerevisiae identifies cellular processes affecting intracellular aggregation of Alzheimer's amyloid-β42: importance of lipid homeostasis.
Authors S Nair, M Traini, I W Dawes, G G Perrone
Abstract Amyloid-β (Aβ)-containing plaques are a major neuropathological feature of Alzheimer's disease (AD). The two major isoforms of Aβ peptide associated with AD are Aβ40 and Aβ42, of which the latter is highly prone to aggregation. Increased presence and aggregation of intracellular Aβ42 peptides is an early event in AD progression. Improved understanding of cellular processes affecting Aβ42 aggregation may have implications for development of therapeutic strategies. Aβ42 fused to green fluorescent protein (Aβ42-GFP) was expressed in ∼4600 mutants of a Saccharomyces cerevisiae genome-wide deletion library to identify proteins and cellular processes affecting intracellular Aβ42 aggregation by assessing the fluorescence of Aβ42-GFP. This screening identified 110 mutants exhibiting intense Aβ42-GFP-associated fluorescence. Four major cellular processes were overrepresented in the data set, including phospholipid homeostasis. Disruption of phosphatidylcholine, phosphatidylserine, and/or phosphatidylethanolamine metabolism had a major effect on intracellular Aβ42 aggregation and localization. Confocal microscopy indicated that Aβ42-GFP localization in the phospholipid mutants was juxtaposed to the nucleus, most likely associated with the endoplasmic reticulum (ER)/ER membrane. These data provide a genome-wide indication of cellular processes that affect intracellular Aβ42-GFP aggregation and may have important implications for understanding cellular mechanisms affecting intracellular Aβ42 aggregation and AD disease progression.
Citation Mol. Biol. Cell 2014; 25:2235-49


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Paper Phenotype Condition Reference Collection Tested mutants Data Details
Nair S~Perrone GG, 2014 expression of human amyloid-beta peptide isoform 42 (Ab42-GFP) expression of amyloid-beta 42 [unknown] hom ~4,600 Discrete

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