ArticleMolecular neurobiology2019
Pathological Modification of TDP-43 in Amyotrophic Lateral Sclerosis with SOD1 Mutations.
Article in Molecular neurobiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 78 citations in OpenAlex.
- SOD1 co-pathologies in the brain: insights from neuropathological evidence and implications.Acta neuropathologica · 2026Review
- Convergent TBK1 loss of function drives gasdermin E dependent pyroptosis and motor neuron degeneration across ALS genotypes.Cell death and differentiation · 2026Article
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- Molecular Modulation of the Crosstalk Between TDP-43 and SOD1.International journal of molecular sciences · 2026Article
- Novel extracellular vesicle release pathway facilitated by toxic superoxide dismutase 1 oligomers.Neurobiology of disease · 2026Article
- Oxidative Stress and Lysosomal Dysfunction in Neurodegenerative Diseases: Underlying Mechanisms and Nanotherapeutic Targeting Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- TDP-43: unveiling the hidden key to cellular fate decisions.Cell communication and signaling : CCS · 2025Review
- Sephin1 reduces TDP-43 cytoplasmic mislocalization and improves motor neuron survival in ALS models.Life science alliance · 2025Article
- Divergent and convergent TMEM106B pathology in murine models of neurodegeneration and human disease.Acta neuropathologica communications · 2025Article
- Trimeric superoxide dismutase 1 antibody as a universal biomarker for ALS.Research square · 2025Article
- Genetic Ablation of Sarm1 Mitigates Disease Acceleration after Traumatic Brain Injury in the SOD1Annals of neurology · 2025Article
- Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.Muscle & nerve · 2025Review
- ALS plasma biomarkers reveal neurofilament and pTau correlate with disease onset and progression.Annals of clinical and translational neurology · 2025Article
- Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice.Molecular neurodegeneration · 2025Article
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- C-reactive protein: the nexus between inflammation and protein misfolding diseases.Frontiers in immunology · 2025Review
- A Review of Biomarkers of Amyotrophic Lateral Sclerosis: A Pathophysiologic Approach.International journal of molecular sciences · 2024Review
- Article
- Neuroprotective effects of ellorarxine in neuronal models of degeneration.Frontiers in neuroscience · 2024Article
- Genetic Landscape of Amyotrophic Lateral Sclerosis in Czech Patients.Journal of neuromuscular diseases · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset, progressive neurodegenerative disorder with no known cure. Cu/Zn-superoxide dismutase (SOD1) was the first identified protein associated with familial ALS (fALS). Recently, TAR DNA-binding protein 43 (TDP-43) has been found to be a principal component of ubiquitinated cytoplasmic inclusions in neurons and glia in ALS. However, it remains unclear whether these ALS-linked proteins partly have a shared pathogenesis. Here, we determine the association between mutant SOD1 and the modification of TDP-43 and the relationship of pathologic TDP-43 to neuronal cytotoxicity in SOD1 ALS. In this work, using animal model, human tissue, and cell models, we provide the evidence that the association between the TDP-43 modification and the pathogenesis of SOD1 fALS. We demonstrated an age-dependent increase in TDP-43 C-terminal fragments and phosphorylation in motor neurons and glia of SOD1 mice and SOD1G85S ALS patient. Cytoplasmic TDP-43 was also observed in iPSC-derived motor neurons from SOD1G17S ALS patient. Moreover, we observed that mutant SOD1 interacts with TDP-43 in co-immunoprecipitation assays with G93A hSOD1-transfected cell lines. Mutant SOD1 overexpression led to an increase in TDP-43 modification in the detergent-insoluble fraction in the spinal cord of SOD1 mice and fALS patient. Additionally, we showed cellular apoptosis in response to the interaction of mutant SOD1 and fragment forms of TDP-43. These findings suggest that mutant SOD1 could affect the solubility/insolubility of TDP-43 through physical interactions and the resulting pathological modifications of TDP-43 may be involved in motor neuron death in SOD1 fALS.
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