‘The awesome power of yeast’ in Alzheimer’s disease research

Abstract

The difficulties in performing experimental studies related to diseases of the human brain have fostered a range of disease models from highly expensive and complex animal models to simple, robust, unicellular yeast models. Yeast models have been used in numerous studies to understand Alzheimer's disease (AD) pathogenesis and to search for drugs targeting AD. Thanks to the conservation of fundamental eukaryotic processes including ageing and the availability of appropriate technological platforms, budding yeast are a simple model eukaryote to assist with understanding human cell biology, offering a platform to study human diseases. This article aims to provide insights from yeast models on the contributions of amyloid beta, a causative agent in AD, and recent research findings on AD chemoprevention.

Simvastatin, Its Antimicrobial Activity and Its Prevention of Alzheimer’s Disease

“…As mentioned previously, yeast cells and human cells share certain biological characteristics. For example, yeast has considerable utility as a model for aging [ 63 ]. Aging yeast and aging human cells show reduced proteostasis, which means that some deleterious proteins accumulate with age.…”

“…In addition, amyloid beta can be visualized by fusing it to fluorescent proteins such as GFP, where it can be observed in cells by fluorescence microscopy [ 65 ]. Examinations of cell populations show that young cells remove amyloid beta fused to GFP, while in older (larger) cells, the amyloid beta fused to GFP persists [ 63 ]. When the yeast is grown in the presence of simvastatin, the levels of amyloid beta or amyloid beta fused to GFP are about 10% of those in untreated cells [ 41 ].…”

The Use of Yeast in Biosensing

“…Reporter systems in yeast biosensors can be based on fluorescence, luminescence, enzymatic reactions (usually measured with a color change in substrates), electrical signal, and growth rate [44]. Interestingly, yeast biosensors can be used to study the status of mitochondrial health, which is unique to yeast and cannot be performed in any other system [48]. Hence, yeast can be used as a biosensor to find chemicals that can modify mitochondrial health.…”

“…Aβ probably has a somewhat non-specific effect on cells, with the deleterious effects being due to its accumulation. By studying yeast with GFP fused to Aβ we observed that in the population, despite all cells producing the fusion protein, young cells remove the fusion protein, so no young cells are fluorescent [48]; however, old cells retained the protein and had green fluorescence. This phenomenon is likely to be due to reduced proteostasis, a phenomenon that is also a significant part of human aging.…”