Alzheimer's Disease: Significant Benefit from the Yeast-Based Models.

Abstract

Alzheimer's disease (AD) is an age-related, multifaceted neurological disorder associated with accumulation of aggregated proteins (amyloid Aβ and hyperphosphorylated tau), loss of synapses and neurons, and alterations in microglia. AD was recognized by the World Health Organization as a global public health priority. The pursuit of a better understanding of AD forced researchers to pay attention to well-defined single-celled yeasts. Yeasts, despite obvious limitations in application to neuroscience, show high preservation of basic biological processes with all eukaryotic organisms and offer great advantages over other disease models due to the simplicity, high growth rates on low-cost substrates, relatively simple genetic manipulations, the large knowledge base and data collections, and availability of an unprecedented amount of genomic and proteomic toolboxes and high-throughput screening techniques, inaccessible to higher organisms. Research reviewed above clearly indicates that yeast models, together with other, more simple eukaryotic models including animal models, C. elegans and Drosophila, significantly contributed to understanding Aβ and tau biology. These models allowed high throughput screening of factors and drugs that interfere with Aβ oligomerization, aggregation and toxicity, and tau hyperphosphorylation. In the future, yeast models will remain relevant, with a focus on creating novel high throughput systems to facilitate the identification of the earliest AD biomarkers among different cellular networks in order to achieve the main goal-to develop new promising therapeutic strategies to treat or prevent the disease.