Trial reportJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2014
Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury.
Trial report in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- TDP-43 as a possible biomarker for frontotemporal lobar degeneration: a systematic review of existing antibodies.Acta neuropathologica communications · 2015Pooled it
- Inhibiting Glycogen Synthase Kinase 3 Suppresses TDP-43-Mediated Neurotoxicity in a Caspase-Dependent Manner.Molecular neurobiology · 2026Article
- Advancements in diagnosing Post-concussion Syndrome: insights into epidemiology, pathophysiology, neuropathology, neuroimaging, and salivary biomarkers.Acta neurologica Belgica · 2025Review
- Repetitive Mild but Not Single Moderate Brain Trauma Is Associated with TAR DNA-Binding Protein 43 Mislocalization and Glial Activation in the Mouse Spinal Cord.Biomedicines · 2025Article
- Article
- CHCHD2 P14L, found in amyotrophic lateral sclerosis, exhibits cytoplasmic mislocalization and alters CaPNAS nexus · 2024Article
- Hetero-oligomerization of TDP-43 carboxy-terminal fragments with cellular proteins contributes to proteotoxicity.Communications biology · 2024Article
- Aberrant mitochondrial aggregation of TDP-43 activated mitochondrial unfolded protein response and contributed to recovery of acetaminophen induced acute liver injury.Toxicology research · 2024Article
- TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.International journal of molecular sciences · 2023Review
- Single Versus Repetitive Traumatic Brain Injury: Current Knowledge on the Chronic Outcomes, Neuropathology and the Role of TDP-43 Proteinopathy.Experimental neurobiology · 2023Review
- Increased Risk of Aging-Related Neurodegenerative Disease after Traumatic Brain Injury.Biomedicines · 2023Review
- Characterization of Calpain and Caspase-6-Generated Glial Fibrillary Acidic Protein Breakdown Products Following Traumatic Brain Injury and Astroglial Cell Injury.International journal of molecular sciences · 2022Article
- Traumatic Brain Injury and Early Onset Dementia in Post 9-11 Veterans.Brain injury · 2022Article
- Generation and Release of Neurogranin, Vimentin, and MBP Proteolytic Peptides, Following Traumatic Brain Injury.Molecular neurobiology · 2022Article
- The Role of Extracellular Matrix Components in the Spreading of Pathological Protein Aggregates.Frontiers in cellular neuroscience · 2022Review
- Differential Expression Patterns of TDP-43 in Single Moderate versus Repetitive Mild Traumatic Brain Injury in Mice.International journal of molecular sciences · 2021Article
- Review
- The Different Faces of the TDP-43 Low-Complexity Domain: The Formation of Liquid Droplets and Amyloid Fibrils.International journal of molecular sciences · 2021Review
- p62 overexpression induces TDP-43 cytoplasmic mislocalisation, aggregation and cleavage and neuronal death.Scientific reports · 2021Article
- Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transactivation response DNA-binding protein 43 (TDP-43) proteinopathy has recently been reported in chronic traumatic encephalopathy, a neurodegenerative condition linked to prior history of traumatic brain injury (TBI). While TDP-43 appears to be vulnerable to proteolytic modifications under neurodegenerative conditions, the mechanism underlying the contribution of TDP-43 to the pathogenesis of TBI remains unknown. In this study, we first mapped out the calpain or caspase-3 TDP-43 fragmentation patterns by in vitro protease digestion. Concurrently, in cultured cerebrocortical neurons subjected to cell death challenges, we identified distinct TDP-43 breakdown products (BDPs) of 35, 33, and 12 kDa that were indicative of dual calpain/caspase attack. Cerebrocortical culture incubated with calpain and caspase-fragmented TDP-43 resulted in neuronal injury. Furthermore, increased TDP-43 BDPs as well as redistributed TDP-43 from the nucleus to the cytoplasm were observed in the mouse cortex in two TBI models: controlled cortical impact injury and overpressure blast-wave-induced brain injury. Finally, TDP-43 and its 35 kDa fragment levels were also elevated in the cerebrospinal fluid (CSF) of severe TBI patients. This is the first evidence that TDP-43 might be involved in acute neuroinjury and TBI pathology, and that TDP-43 and its fragments may have biomarker utilities in TBI patients.
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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.