A rapid absorbance-based growth assay to screen the toxicity of oligomer Aβ42 and protection against cell death in yeast

Prashant Bharadwaj*, Ralph Martins

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Multiple lines of evidence show that soluble oligomer forms of amyloid β protein (Aβ42) are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer's disease. Although many studies have used mammalian cells to investigate oligomer Aβ42 toxicity, the use of more simple eukaryotic cellular systems offers advantages for large-scale screening studies. We have previously established and validated budding yeast, Saccharomyces cerevisiae to be a simple and a robust model to study the toxicity of Aβ. Using colony counting based methods, oligomeric Aβ42 was shown to induce dose-dependent cell death in yeast. We have adapted this method for high throughput screening by developing an absorbance-based growth assay. We further validated the assay with treatments previously shown to protect oligomer Aβ42 induced cell death in mammalian and yeast cells. This assay offers a platform for studying underlying mechanisms of oligomer Aβ42 induced cell death using gene deletion/overexpression libraries and developing novel agents that alleviate Aβ42 induced cell death.

Original languageEnglish
Pages (from-to)1931-1936
Number of pages6
JournalNeural Regeneration Research
Volume15
Issue number10
DOIs
Publication statusPublished - 1 Oct 2020

Bibliographical note

Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

A corrigendum exists for this article, and can be found in Neural Regeneration Research (2020) Vol 15(11) p. 2161, at doi: 10.4103/1673-5374.282273

Keywords

  • Alzheimer’s disease
  • amyloid toxicity
  • autophagy
  • Aβ42 oligomer
  • high-throughput screening
  • latrepirdine
  • neuroprotection
  • yeast model

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