Validation of folate in a convenient yeast assay suited for identification of inhibitors of Alzheimer's amyloid-beta aggregation.
Previously in the search for chemopreventatives for Alzheimer's disease (AD), microbial cells with amyloid-beta (Abeta) protein fusions have been used to screen for compounds that reduce the aggregation, misfolding or oligomerization of Abeta. In the current study, such a system has been used to look at the effect of folate, whose deficiency has been associated with AD. A folate-deficient yeast strain producing Abeta fused to green fluorescent protein (GFP) that spontaneously misfolds/aggregates and suppresses green fluorescence was used to examine the effects of folinic acid on Abeta-GFP fluorescence. At levels that did not affect growth or plasmid stability, increasing levels of folinic acid led to increasing green fluorescence, suggesting folate can assist with preventing Abeta-misfolding/aggregation. This result supports a protective role for folate and suggests that yeast assays may provide significant new approaches for testing of AD chemopreventatives.
Macreadie
Ian
I
CSIRO Molecular and Health Technologies and P-Health Flagship, Parkville, VIC, Australia. ian.macreadie@csiro.au
Lotfi-Miri
Mehrnoush
M
Mohotti
Sameera
S
Shapira
Deborah
D
Bennett
Louise
L
Varghese
Joseph
J
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000187:drug effects*; D001681:Biological Assay; D005434:Flow Cytometry; D005492:Folic Acid / Q000032:analysis*; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000235:genetics; D002955:Leucovorin / Q000494:pharmacology; D010453:Peptide Synthases / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017510:Protein Folding / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D014803:Vitamin B Complex / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D014803:Vitamin B Complex; D049452:Green Fluorescent Proteins; D005492:Folic Acid; D010453:Peptide Synthases; C020041:dihydrofolate synthetase; D002955:Leucovorin