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Article type: Research Article
Authors: Macreadie, Iana; * | Lotfi-Miri, Mehrnousha | Mohotti, Sameeraa; b | Shapira, Deboraha | Bennett, Louisea; c | Varghese, Josepha
Affiliations: [a] CSIRO Molecular and Health Technologies and P-Health Flagship, Parkville, VIC, Australia | [b] RMIT University, Bundoora, VIC, Australia | [c] Food Science Australia, Werribee, VIC, Australia
Correspondence: [*] Corresponding author: Prof Ian G. Macreadie, CSIRO Molecular and Health Technologies, 343 Royal Parade, Parkville, VIC 3052, Australia. Tel.: +61 3 9662 7299; Fax: +61 3 9662 7266; Mob: 0402 564 308; E-mail: [email protected].
Abstract: Previously in the search for chemopreventatives for Alzheimer's disease (AD), microbial cells with amyloid-β (Aβ) protein fusions have been used to screen for compounds that reduce the aggregation, misfolding or oligomerization of Aβ. 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 Aβ fused to green fluorescent protein (GFP) that spontaneously misfolds/aggregates and suppresses green fluorescence was used to examine the effects of folinic acid on Aβ-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 Aβ-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.
Keywords: Aggregation, Alzheimer's disease chemo preventatives, amyloid-β, flow cytometry, folate, high throughput screening, oligomerization, Saccharomyces cerevisiae, yeast assays
DOI: 10.3233/JAD-2008-15305
Journal: Journal of Alzheimer's Disease, vol. 15, no. 3, pp. 391-396, 2008
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