ArticleHuman molecular genetics2015
PABPN1 suppresses TDP-43 toxicity in ALS disease models.
Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Exosome Proteomics of SOD1Annals of clinical and translational neurology · 2026Article
- PABPN1 Couples the Polyadenylation and Translation of Maternal Transcripts to Mouse Oocyte Meiotic Maturation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Twist in Yeast: New Perspectives for Studying TDP-43 Proteinopathies inJournal of fungi (Basel, Switzerland) · 2025Review
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
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- Article
- Human herpesvirus 8 ORF57 protein is able to reduce TDP-43 pathology: network analysis identifies interacting pathways.Human molecular genetics · 2023Article
- Nuclear import receptors are recruited by FG-nucleoporins to rescue hallmarks of TDP-43 proteinopathy.Molecular neurodegeneration · 2022Article
- Fly for ALS: Drosophila modeling on the route to amyotrophic lateral sclerosis modifiers.Cellular and molecular life sciences : CMLS · 2021Review
- The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils.International journal of molecular sciences · 2021Review
- Molecular Mechanisms Underlying TDP-43 Pathology in Cellular and Animal Models of ALS and FTLD.International journal of molecular sciences · 2021Review
- Amyotrophic Lateral Sclerosis Genes inInternational journal of molecular sciences · 2021Review
- Stress Granule Assembly Can Facilitate but Is Not Required for TDP-43 Cytoplasmic Aggregation.Biomolecules · 2020Article
- Proteomic analysis reveals that wildtype and alanine-expanded nuclear poly(A)-binding protein exhibit differential interactions in skeletal muscle.The Journal of biological chemistry · 2019Article
- The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: a resolution in sight?Brain : a journal of neurology · 2019Review
- The Pathobiology of TDP-43 C-Terminal Fragments in ALS and FTLD.Frontiers in neuroscience · 2019Review
- TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD.Nature neuroscience · 2018Article
- Nuclear poly(A) binding protein 1 (PABPN1) and Matrin3 interact in muscle cells and regulate RNA processing.Nucleic acids research · 2017Article
- RNA-binding proteins implicated in neurodegenerative diseases.Wiley interdisciplinary reviews. RNA · 2017Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
TAR DNA-binding protein 43 (TDP-43) is a major disease protein in amyotrophic lateral sclerosis (ALS) and related neurodegenerative diseases. Both the cytoplasmic accumulation of toxic ubiquitinated and hyperphosphorylated TDP-43 fragments and the loss of normal TDP-43 from the nucleus may contribute to the disease progression by impairing normal RNA and protein homeostasis. Therefore, both the removal of pathological protein and the rescue of TDP-43 mislocalization may be critical for halting or reversing TDP-43 proteinopathies. Here, we report poly(A)-binding protein nuclear 1 (PABPN1) as a novel TDP-43 interaction partner that acts as a potent suppressor of TDP-43 toxicity. Overexpression of full-length PABPN1 but not a truncated version lacking the nuclear localization signal protects from pathogenic TDP-43-mediated toxicity, promotes the degradation of pathological TDP-43 and restores normal solubility and nuclear localization of endogenous TDP-43. Reduced levels of PABPN1 enhances the phenotypes in several cell culture and Drosophila models of ALS and results in the cytoplasmic mislocalization of TDP-43. Moreover, PABPN1 rescues the dysregulated stress granule (SG) dynamics and facilitates the removal of persistent SGs in TDP-43-mediated disease conditions. These findings demonstrate a role for PABPN1 in rescuing several cytopathological features of TDP-43 proteinopathy by increasing the turnover of pathologic proteins.
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Registered trials
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