A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>

TAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation of the TDP-43 protein in neurons and glial cells. These proteinopathies are associated with several NDs, including amyotrophic lateral sclerosis, frontot...

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Main Authors: Roberto Stella, Alessandro Bertoli, Raffaele Lopreiato, Caterina Peggion
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Journal of Fungi
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Online Access:https://www.mdpi.com/2309-608X/11/3/188
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author Roberto Stella
Alessandro Bertoli
Raffaele Lopreiato
Caterina Peggion
author_facet Roberto Stella
Alessandro Bertoli
Raffaele Lopreiato
Caterina Peggion
author_sort Roberto Stella
collection DOAJ
description TAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation of the TDP-43 protein in neurons and glial cells. These proteinopathies are associated with several NDs, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and some forms of Alzheimer’s disease. Yeast models have proven valuable in ND research due to their simplicity, genetic tractability, and the conservation of many cellular processes shared with higher eukaryotes. For several decades, <i>Saccharomyces cerevisiae</i> has been used as a model organism to study the behavior and toxicity of TDP-43, facilitating the identification of genes and pathways that either exacerbate or mitigate its toxic effects. This review will discuss evidence showing that yeast models of TDP-43 exhibit defects in proteostasis, mitochondrial function, autophagy, and RNA metabolism, which are key features of TDP-43-related NDs. Additionally, we will explore how modulating proteins involved in these processes reduce TDP-43 toxicity, aiding in restoring normal TDP-43 function or preventing its pathological aggregation. These findings highlight potential therapeutic targets for the treatment of TDP-43-related diseases.
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spelling doaj-art-caa7042a2bf147d7a896a1adee54a3cc2025-08-20T01:48:46ZengMDPI AGJournal of Fungi2309-608X2025-02-0111318810.3390/jof11030188A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>Roberto Stella0Alessandro Bertoli1Raffaele Lopreiato2Caterina Peggion3Laboratorio Farmaci Veterinari e Ricerca, Istituto Zooprofilattico Sperimentale delle Venezie, 35020 Legnaro, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biomedical Sciences, University of Padova, 35131 Padova, ItalyDepartment of Biology, University of Padova, 35131 Padova, ItalyTAR DNA-binding protein 43 kDa (TDP-43) proteinopathies are a group of neurodegenerative diseases (NDs) characterized by the abnormal accumulation of the TDP-43 protein in neurons and glial cells. These proteinopathies are associated with several NDs, including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and some forms of Alzheimer’s disease. Yeast models have proven valuable in ND research due to their simplicity, genetic tractability, and the conservation of many cellular processes shared with higher eukaryotes. For several decades, <i>Saccharomyces cerevisiae</i> has been used as a model organism to study the behavior and toxicity of TDP-43, facilitating the identification of genes and pathways that either exacerbate or mitigate its toxic effects. This review will discuss evidence showing that yeast models of TDP-43 exhibit defects in proteostasis, mitochondrial function, autophagy, and RNA metabolism, which are key features of TDP-43-related NDs. Additionally, we will explore how modulating proteins involved in these processes reduce TDP-43 toxicity, aiding in restoring normal TDP-43 function or preventing its pathological aggregation. These findings highlight potential therapeutic targets for the treatment of TDP-43-related diseases.https://www.mdpi.com/2309-608X/11/3/188TDP-43neurodegenerationRNA metabolismprotein aggregationALSchaperone
spellingShingle Roberto Stella
Alessandro Bertoli
Raffaele Lopreiato
Caterina Peggion
A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
Journal of Fungi
TDP-43
neurodegeneration
RNA metabolism
protein aggregation
ALS
chaperone
title A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
title_full A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
title_fullStr A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
title_full_unstemmed A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
title_short A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies in <i>S. cerevisiae</i>
title_sort twist in yeast new perspectives for studying tdp 43 proteinopathies in i s cerevisiae i
topic TDP-43
neurodegeneration
RNA metabolism
protein aggregation
ALS
chaperone
url https://www.mdpi.com/2309-608X/11/3/188
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