Modeling ALS and FTLD proteinopathies in yeast: An efficient approach for studying protein aggregation and toxicity

Kryndushkin, Dmitry; Shewmaker, Frank

doi:10.4161/pri.5.4.17229

Cited by 2 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Approximately 6,000 human genes have yeast homologs; about 10% of which can be complemented by (or can complement) their yeast counterpart in vivo (Cherry et al, 2012). About 500 human disease genes have yeast orthologs (Kryndushkin and Shewmaker, 2011). The most straightforward approach to looking at human disease genes in yeast is in situations when the gene complements a yeast ortholog.…”

Section: Introductionmentioning

confidence: 99%

“…The most straightforward approach to looking at human disease genes in yeast is in situations when the gene complements a yeast ortholog. This is the case for SOD1, in which human mutants can be quickly assayed for their ability to complement the yeast ortholog (Kryndushkin and Shewmaker, 2011). Unfortunately, most neurodegenerative disease-causing proteins do not have yeast orthologs, thus making their study more challenging.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Yeast Models of Prion-Like Proteins That Cause Amyotrophic Lateral Sclerosis Reveal Pathogenic Mechanisms

Monahan

Rhoads

Yee

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Many proteins involved in the pathogenic mechanisms of amyotrophic lateral sclerosis (ALS) are remarkably similar to proteins that form prions in the yeast Saccharomyces cerevisiae. These ALS-associated proteins are not orthologs of yeast prion proteins, but are similar in having long, intrinsically disordered domains that are rich in hydrophilic amino acids. These so-called prion-like domains are particularly aggregation-prone and are hypothesized to participate in the mislocalization and misfolding processes that occur in the motor neurons of ALS patients. Methods developed for characterizing yeast prions have been adapted to studying ALS-linked proteins containing prion-like domains. These yeast models have yielded major discoveries, including identification of new ALS genetic risk factors, new ALS-causing gene mutations and insights into how disease mutations enhance protein aggregation.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Yeast Models of Prion-Like Proteins That Cause Amyotrophic Lateral Sclerosis Reveal Pathogenic Mechanisms

Monahan

Rhoads

Yee

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Despite unicellular models not being able to recapitulate complex disease phenotypes for certain, the completely sequenced genome [ 86 ] and the presence of an ortholog for many human disease genes [ 87 ] render the eukaryote budding yeast Saccharomyces cerevisiae a good candidate for where to model different pathologies [ 88 , 89 , 90 ]. As such, this model organism has been used to set up pioneering experiments identifying several different ALS genetic modifiers.…”

Section: Modeling Als In Different Systemsmentioning

confidence: 99%

“…FUS ectopic overexpression in yeast inhibits the ubiquitin-proteasome system [ 97 ] and determines the formation of toxic cytoplasmic aggregates that co-localize with P-bodies and stress granules [ 24 , 87 , 98 , 99 ]. Removing the RNA recognition motif of FUS does not act on aggregates production but rescues FUS-induced toxicity, thus highlighting that the interaction between FUS and RNA is essential for FUS toxic action [ 98 ].…”

Section: Modeling Als In Different Systemsmentioning

confidence: 99%

Where and Why Modeling Amyotrophic Lateral Sclerosis

Liguori

Amadio

Volonté

2021

IJMS

View full text Add to dashboard Cite

Over the years, researchers have leveraged a host of different in vivo models in order to dissect amyotrophic lateral sclerosis (ALS), a neurodegenerative/neuroinflammatory disease that is heterogeneous in its clinical presentation and is multigenic, multifactorial and non-cell autonomous. These models include both vertebrates and invertebrates such as yeast, worms, flies, zebrafish, mice, rats, guinea pigs, dogs and, more recently, non-human primates. Despite their obvious differences and peculiarities, only the concurrent and comparative analysis of these various systems will allow the untangling of the causes and mechanisms of ALS for finally obtaining new efficacious therapeutics. However, harnessing these powerful organisms poses numerous challenges. In this context, we present here an updated and comprehensive review of how eukaryotic unicellular and multicellular organisms that reproduce a few of the main clinical features of the disease have helped in ALS research to dissect the pathological pathways of the disease insurgence and progression. We describe common features as well as discrepancies among these models, highlighting new insights and emerging roles for experimental organisms in ALS.

show abstract

Modeling ALS and FTLD proteinopathies in yeast: An efficient approach for studying protein aggregation and toxicity

Cited by 2 publications

References 42 publications

Yeast Models of Prion-Like Proteins That Cause Amyotrophic Lateral Sclerosis Reveal Pathogenic Mechanisms

Yeast Models of Prion-Like Proteins That Cause Amyotrophic Lateral Sclerosis Reveal Pathogenic Mechanisms

Where and Why Modeling Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About