Prions

Kryndushkin, Dmitry; Edskes, Herman K.; Shewmaker, Frank; Wickner, Reed B.

doi:10.1101/pdb.top077586

Cited by 4 publications

(3 citation statements)

References 68 publications

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“…Yeast prions are endogenous heritable amyloids, most often studied in the yeast Saccharomyces cerevisiae [12,13,14,15]. The molecular foundation of inheritance for yeast prions and mammalian amyloids is through nucleated polymerization of amyloid fibrils.…”

Section: Yeast Prions and Protein Quality Controlmentioning

confidence: 99%

“…The phenotypic effects of prion formation are typically manifested as a decrease of protein function in the amyloid state. Due to convenient genetic and phenotypic assays, yeast prions provide a useful model system for studying mechanisms of amyloid formation and propagation that are mostly applicable to mammalian and human diseases [12,13,14,15].…”

Section: Yeast Prions and Protein Quality Controlmentioning

confidence: 99%

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Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery

2019

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Amyloids are self-perpetuating protein aggregates causing neurodegenerative diseases in mammals. Prions are transmissible protein isoforms (usually of amyloid nature). Prion features were recently reported for various proteins involved in amyloid and neural inclusion disorders. Heritable yeast prions share molecular properties (and in the case of polyglutamines, amino acid composition) with human disease-related amyloids. Fundamental protein quality control pathways, including chaperones, the ubiquitin proteasome system and autophagy are highly conserved between yeast and human cells. Crucial cellular proteins and conditions influencing amyloids and prions were uncovered in the yeast model. The treatments available for neurodegenerative amyloid-associated diseases are few and their efficiency is limited. Yeast models of amyloid-related neurodegenerative diseases have become powerful tools for high-throughput screening for chemical compounds and FDA-approved drugs that reduce aggregation and toxicity of amyloids. Although some environmental agents have been linked to certain amyloid diseases, the molecular basis of their action remains unclear. Environmental stresses trigger amyloid formation and loss, acting either via influencing intracellular concentrations of the amyloidogenic proteins or via heterologous inducers of prions. Studies of environmental and physiological regulation of yeast prions open new possibilities for pharmacological intervention and/or prophylactic procedures aiming on common cellular systems rather than the properties of specific amyloids.

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Section: Yeast Prions and Protein Quality Controlmentioning

confidence: 99%

Section: Yeast Prions and Protein Quality Controlmentioning

confidence: 99%

Yeast Models for Amyloids and Prions: Environmental Modulation and Drug Discovery

2019

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“…2c. Furthermore, we believe that such macroscopic approaches, as reviewed here, will enable more realistic accounting of the behavior of amyloids in living organisms, such as the yeast amyloid model systems used to study the epigenetic aspects of amyloid prions (Edskes et al 2017;Wickner et al 2015;Kryndushkin et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Unified theoretical description of the kinetics of protein aggregation

Hirota¹,

Edskes²,

Hall

2019

Biophys Rev

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Solution conditions chosen for the production of amyloid can also promote formation of significant extents of amorphous protein aggregate. In one interpretation, the amyloid and amorphous aggregation pathways are considered to be in competition with each other. An alternative conceptualization involves considering amorphous aggregation as an obligatory intermediate process of the amyloid formation pathway. Here, we review recently developed macroscopic-level theories of protein aggregation that unify these two competing models into a single paradigm. Key features of the unified model included (1) a description of the amorphous aggregate as a second liquid phase with the degree of liquid-like character determined by the mobility of the monomer within it, and (2) heterogeneous growth pathways based on nucleation, growth, and fragmentation of amyloid occurring within different phases and at their interfacial boundary. Limiting-case behaviors of the protein aggregation reaction, either singly involving amyloid or amorphous aggregate production, and mixed-case behaviors, involving competitive and/or facilitated growth of amorphous and amyloid species, are presented and reviewed in context. This review principally describes an approach developed by Hall 2019 (Hirota, N. andHall, D. 2019. Protein Aggregation Kinetics: A Unified Theoretical Description. Chapter 7 of 'Protein Solubility and Amorphous Aggregation: From Academic Research to Applications in Drug Discovery and Bioindustry' edited by Y. Kuroda and F. Arisaka. CMC Publishers). Sections of that work are translated from the original Japanese and republished here with the full permission of CMC Publishing Corporation.

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