ArticleMolecular brain2015
Ubiquilin-2 drives NF-κB activity and cytosolic TDP-43 aggregation in neuronal cells.
Article in Molecular brain, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 63 citations in OpenAlex.
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- UBQLN2 in neurodegenerative disease: mechanistic insights and emerging therapeutic potential.Biochemical Society transactions · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.Nature reviews. Neurology · 2024Review
- Epigenetics in the formation of pathological aggregates in amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- UBQLN2 undergoes a reversible temperature-induced conformational switch that regulates binding with HSPA1B: ALS/FTD mutations cripple the switch but do not destroy HSPA1B binding.Biochimica et biophysica acta. General subjects · 2023Article
- Study of Ubiquitin Pathway Genes in a French Population with Amyotrophic Lateral Sclerosis: Focus onInternational journal of molecular sciences · 2023Article
- The identification of high-preforming antibodies for Ubiquilin-2 for use in Western Blot, immunoprecipitation, and immunofluorescence.F1000Research · 2023Article
- Damaged DNA Is an Early Event of Neurodegeneration in Induced Pluripotent Stem Cell-Derived Motoneurons with UBQLN2International journal of molecular sciences · 2022Article
- SHARPIN: Role in Finding NEMO and in Amyloid-Beta Clearance and Degradation (ABCD) Pathway in Alzheimer's Disease?Cellular and molecular neurobiology · 2022Review
- Autophagy Dysfunction in ALS: from Transport to Protein Degradation.Journal of molecular neuroscience : MN · 2022Review
- Review
- Regulation of neuronal autophagy and the implications in neurodegenerative diseases.Neurobiology of disease · 2022Review
- ALS-linked mutations impair UBQLN2 stress-induced biomolecular condensate assembly in cells.Journal of neurochemistry · 2021Article
- Review
- Role of NF-κB in Ageing and Age-Related Diseases: Lessons from Genetically Modified Mouse Models.Cells · 2021Review
- TDP-43 and Inflammation: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.International journal of molecular sciences · 2021Review
- The Links between ALS and NF-κB.International journal of molecular sciences · 2021Review
- Targeting TDP-43 Pathology Alleviates Cognitive and Motor Deficits Caused by Chronic Cerebral Hypoperfusion.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- The role of sequestosome 1/p62 protein in amyotrophic lateral sclerosis and frontotemporal dementia pathogenesis.Neural regeneration research · 2020Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundMutations in the gene encoding Ubiquilin-2 (UBQLN2) are linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). UBQLN2 plays a central role in ubiquitin proteasome system (UPS) and UBQLN2 mutants can form cytoplasmic aggregates in vitro and in vivo.
resultsHere, we report that overexpression of WT or mutant UBQLN2 species enhanced nuclear factor κB (NF-κB) activation in Neuro2A cells. The inhibition of NF-κB stress-mediated activation with SB203580, a p38 MAPK inhibitor, demonstrated a role for MAPK in NF-κB activation by UBQLN2 species. Live cell imaging and microscopy showed that UBQLN2 aggregates are dynamic structures that promote cytoplasmic accumulation of TAR DNA-binding protein (TDP-43), a major component of ALS inclusion bodies. Furthermore, up-regulation of UBQLN2 species in neurons caused an ER-stress response and increased their vulnerability to death by toxic mediator TNF-α. Withaferin A, a known NF-κB inhibitor, reduced mortality of Neuro2A cells overexpressing UBQLN2 species.
conclusionsThese results suggest that UBQLN2 dysregulation in neurons can drive NF-κB activation and cytosolic TDP-43 aggregation, supporting the concept of pathway convergence in ALS pathogenesis. These Ubiquilin-2 pathogenic pathways might represent suitable therapeutic targets for future ALS treatment.
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