ArticleInternational journal of molecular sciences2022
Characterization of Calpain and Caspase-6-Generated Glial Fibrillary Acidic Protein Breakdown Products Following Traumatic Brain Injury and Astroglial Cell Injury.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Exploiting blood-based biomarkers to align preclinical models with human traumatic brain injury.Brain : a journal of neurology · 2025Pooled it
- Temporal profiling of hippocampal astrocyte reactivity reveals persistent GFAP cleavage and complement C3 association after status epilepticus.Brain structure & function · 2026Article
- GFAP degradation in TBI: linking novel modified products to astrocyte pathology and patient outcome.Acta neuropathologica communications · 2026Article
- Plasma biomarker trajectories across Alzheimer's clinical onset: a 17-year prospective study.Alzheimer's research & therapy · 2026Article
- The Dynamics of Neuroinflammation in Traumatic Brain Injury: Molecular Markers Useful for Establishing the Post-Traumatic Interval in Forensic Practice.International journal of molecular sciences · 2026Review
- The Role of Glial Fibrillary Acidic Protein in the Neuropathology of Alzheimer's Disease and Its Potential as a Blood Biomarker for Early Diagnosis and Progression.Molecular neurobiology · 2025Review
- Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD.Neurology international · 2025Review
- Translational Outcomes Project in Neurotrauma (TOP-NT) Pre-Clinical Consortium Study: A Synopsis.Journal of neurotrauma · 2025Article
- Deletions in Glial Fibrillary Acidic Protein Leading to Alterations in Intermediate Filament Assembly and Network Formation.International journal of molecular sciences · 2025Article
- Novel insights into the molecular nature of neurofilament light polypeptide species in cerebrospinal fluid.Brain communications · 2025Article
- The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.Journal of neurochemistry · 2025Review
- Circulating Brain-Reactive Autoantibody Profiles in Military Breachers Exposed to Repetitive Occupational Blast.International journal of molecular sciences · 2024Article
- The RhoB p.S73F mutation leads to cerebral palsy through dysregulation of lipid homeostasis.EMBO molecular medicine · 2024Article
- GFAP as Astrocyte-Derived Extracellular Vesicle Cargo in Acute Ischemic Stroke Patients-A Pilot Study.International journal of molecular sciences · 2024Article
- Functional Selection of Tau Oligomerization-Inhibiting Aptamers.Angewandte Chemie (International ed. in English) · 2024Article
- Stability dynamics of neurofilament and GFAP networks and protein fragments.Current opinion in cell biology · 2023Review
- Regional variances depict a unique glial-specific inflammatory response following closed-head injury.Frontiers in cellular neuroscience · 2023Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites at A-56*A-61 and (ii) major C-terminal cleavage sites at T-383*Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78/R-79 and D-225/A-226, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.
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Registered trials
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