In 2001, a collection of isogenic yeast strains, each deleted for one of the 6000 putative open reading frames (ORFs), was created. Haploidy implies that gene-knockout strains can easily be obtained. Spores can then later give rise to haploid cells. Mating leads to the formation of a diploid cell that can either continue to exist and bud as a diploid or, under conditions of stress, produce spores by meiosis. Haploids are of 2 different mating type (a or α) and a haploid cell can only mate with a cell of the opposite mating type. Yeast reproduction is through mitosis of either a haploid or a diploid cell. Beyond the laboratory yeast strains, many different natural, brewery and clinical isolates exist and all have a core genome of about 5000 shared genes. Since then, it has been estimated that nearly 31% of yeast genes have human orthologues. With more than 6000 genes distributed on 16 chromosomes, its genome was the first eukaryotic genome to be completely sequenced in 1996. cerevisiae is a very widely studied single-celled model organism. However, yeast cell models are playing an increasingly important role in unravelling the fundamental disease aspects of AD. Studies to gain more insights on AD primarily make use of human cell lines and transgenic mouse models. Widespread experimental evidence also suggests that AD is characterized by synaptic dysfunction early on in the disease process, disrupting communication within neural circuits important for memory formation and other cognitive functions such as intellectuality and comprehensive capacity. At the cellular level, AD is characterized by an irreversible and progressive loss of neuronal structure and function within certain regions of the brain including the hippocampus and neocortical brain, leading to cognitive dysfunction and dementia. Currently, around 50 million individuals live with this devastating chronic disease and it has been estimated that the number will increase up to approximately 106 million people by 2050 due to an increasing aging population. It accounts for approximately 60–70% of all dementia cases and affects about 6% of the population aged over 65 (late-onset AD), whereas 2–10% of patients suffer from early-onset AD. Finally, traditional and more innovative research methodologies, e.g., for studying protein oligomerization/aggregation, are highlighted.Īlzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. ![]() In addition to well-established Saccharomyces cerevisiae models, new upcoming Schizosaccharomyces pombe, Candida glabrata and Kluyveromyces lactis yeast models for Aβ and Tau are briefly described. Moreover, these yeast models have also shown their importance in translational research, e.g., in compound screenings and for AD diagnostics development. Despite having limitations with regard to intercellular and cognitive AD aspects, these models have clearly shown their added value as complementary models for the study of the molecular aspects of these proteins, including their interplay with AD-related cellular processes such as mitochondrial dysfunction and altered proteostasis. In this review article, yeast model-based research advances regarding the role of Amyloid-β (Aβ), Tau and frameshift Ubiquitin UBB +1 in Alzheimer’s disease (AD) are discussed.
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