Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(Aβ42)are the most neurotoxic species in the brain and correlates with the degree of neuronal loss and cognitive deficit in Alzheimer’s ...Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(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.展开更多
Alzheimer’s disease（AD）is the most common form of age-related dementia with the latest report（World Alzheimer Report,2015）showing 46.8 million people are currently affected by dementia.That number is expected to ...Alzheimer’s disease（AD）is the most common form of age-related dementia with the latest report（World Alzheimer Report,2015）showing 46.8 million people are currently affected by dementia.That number is expected to double every 20 years unless there is effective therapeutic intervention.The 42 amino acid peptide known as amyloid beta（or Aβ）has been implicated as one of the main causative agents of AD after its discovery in plaques in 1985（Masters et al.,1985）.展开更多
基金supported by the National Health and Medical Research Council-Australian Research Council dementia research development fellowship(APP1107109)to PB
文摘Multiple lines of evidence show that soluble oligomer forms of amyloidβprotein(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.
文摘Alzheimer’s disease（AD）is the most common form of age-related dementia with the latest report（World Alzheimer Report,2015）showing 46.8 million people are currently affected by dementia.That number is expected to double every 20 years unless there is effective therapeutic intervention.The 42 amino acid peptide known as amyloid beta（or Aβ）has been implicated as one of the main causative agents of AD after its discovery in plaques in 1985（Masters et al.,1985）.
