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. © 2020 Neural Regeneration Research. All rights reserved.
RAS ID
31551
Document Type
Journal Article
Date of Publication
1-1-2020
Funding Information
National Health and Medical Research Council, NHMRC
School
Centre of Excellence for Alzheimer’s Disease Research and Care / School of Medical and Health Sciences
Grant Number
NHMRC Number : 1107109
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.
Publisher
Wolters Kluwer
Comments
Bharadwaj, P., & Martins, R. (2020). A rapid absorbance-based growth assay to screen the toxicity of oligomer Aβ42 and protect against cell death in yeast. Neural Regeneration Research, 15(10), Article 1931. https://doi.org/10.4103/1673-5374.280318