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.

Kcs1 and Vip1: The Key Enzymes behind Inositol Pyrophosphate Signaling in Saccharomyces cerevisiae

“…The study of the PP-IP pathway may provide valuable insights into alleviating neurodegenerative diseases [66][67][68]. One such disease is Alzheimer's, a neurodegenerative condition characterized by the accumulation of amyloid plaques (composed of amyloidbeta peptides) and neurofibrillary tangles (composed of hyperphosphorylated Tau proteins) [69].…”

Saccharomyces cerevisiae as a Model for Studying Human Neurodegenerative Disorders: Viral Capsid Protein Expression

“…This chapter will summarize the available experimental data on the aggregation in yeast cells of proteins whose aggregation has been identified in studies of human NDs, such as polyglutamine proteins, α-synuclein, TDP-4, FUS, SOD1, and tau (see Table 1). However, we will not discuss data on the Aβ protein associated with Alzheimer's disease, as several excellent reviews have recently addressed specific aspects of Alzheimer's diseases using yeast models [28,[42][43][44][45][46]. In addition, this review will not discuss studies related to prion proteins because, in our view, prions are a special type of protein, and summarizing the results related to their study requires separate consideration.…”