ArticleThe Journal of biological chemistry2009
Potentiation of amyotrophic lateral sclerosis (ALS)-associated TDP-43 aggregation by the proteasome-targeting factor, ubiquilin 1.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.Frontiers in physiology · 2020Pooled it
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Presenilin: A Multi-Functional Molecule in the Pathogenesis of Alzheimer's Disease and Other Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Invertebrate genetic models of amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Cytoplasmic TDP-43 is involved in cell fate during stress recovery.Human molecular genetics · 2021Article
- Marine Neurotoxins' Effects on Environmental and Human Health: An OMICS Overview.Marine drugs · 2021Review
- Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling.Oncology reports · 2021Article
- Lysosome dysfunction as a cause of neurodegenerative diseases: Lessons from frontotemporal dementia and amyotrophic lateral sclerosis.Neurobiology of disease · 2021Review
- Mitochondrion-Dependent Cell Death in TDP-43 Proteinopathies.Biomedicines · 2021Review
- A Novel Supplement Attenuates Oxidative Stress-Induced TDP-43-Related Pathogenesis in TDP-43-Expressed Cells.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Stress granule subtypes: an emerging link to neurodegeneration.Cellular and molecular life sciences : CMLS · 2020Review
- Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery.The Biochemical journal · 2020Review
- TDP-43, a protein central to amyotrophic lateral sclerosis, is destabilized by tankyrase-1 and -2.Journal of cell science · 2020Article
- On the Neuroprotective Effects of Naringenin: Pharmacological Targets, Signaling Pathways, Molecular Mechanisms, and Clinical Perspective.Biomolecules · 2019Review
- TDP-43 proteinopathy and mitochondrial abnormalities in neurodegeneration.Molecular and cellular neurosciences · 2019Review
- TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response.PLoS genetics · 2019Article
- The debated toxic role of aggregated TDP-43 in amyotrophic lateral sclerosis: a resolution in sight?Brain : a journal of neurology · 2019Review
- Non-Proteasomal UbL-UbA Family of Proteins in Neurodegeneration.International journal of molecular sciences · 2019Review
- Epigenetics in amyotrophic lateral sclerosis: a role for histone post-translational modifications in neurodegenerative disease.Translational research : the journal of laboratory and clinical medicine · 2019Review
- Molecular Mechanisms of TDP-43 Misfolding and Pathology in Amyotrophic Lateral Sclerosis.Frontiers in molecular neuroscience · 2019Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
TDP-43 (43-kDa TAR DNA-binding domain protein) is a major constituent of ubiquitin-positive cytoplasmic aggregates present in neurons of patients with fronto-temporal lobular dementia and amyotrophic lateral sclerosis (ALS). The pathologic significance of TDP-43 aggregation is not known; however, dominant mutations in TDP-43 cause a subset of ALS cases, suggesting that misfolding and/or altered trafficking of TDP-43 is relevant to the disease process. Here, we show that the presenilin-binding protein ubiquilin 1 (UBQLN) plays a role in TDP-43 aggregation. TDP-43 interacted with UBQLN both in yeast and in vitro, and the carboxyl-terminal ubiquitin-associated domain of UBQLN was both necessary and sufficient for binding to polyubiquitylated forms of TDP-43. Overexpression of UBQLN recruited TDP-43 to detergent-resistant cytoplasmic aggregates that colocalized with the autophagosomal marker, LC3. UBQLN-dependent aggregation required the UBQLN UBA domain, was mediated by non-overlapping regions of TDP-43, and was abrogated by a mutation in UBQLN previously linked to Alzheimer disease. Four ALS-associated alleles of TDP-43 also coaggregated with UBQLN, and the extent of aggregation correlated with in vitro UBQLN binding affinity. Our findings suggest that UBQLN is a polyubiquitin-TDP-43 cochaperone that mediates the autophagosomal delivery and/or proteasome targeting of TDP-43 aggregates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.