ArticleJournal of neuroinflammation2015
Granzyme B-inhibitor serpina3n induces neuroprotection in vitro and in vivo.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 90 citations in OpenAlex.
- Rethinking the Oligodendrocyte Progenitor Cell: One Cell, Many Functions.The European journal of neuroscience · 2026Review
- Injury-transduced oligodendrocytes modulate neuroinflammation and glial activation in diseased and non-diseased central nervous system.Nature communications · 2026Article
- Serum SERPINA3 as a Candidate Non-Invasive Biomarker for Neuromyelitis Optica Spectrum Disorder: Proteomic Discovery and Same-Center Validation.Diagnostics (Basel, Switzerland) · 2026Article
- Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.Acta neuropathologica · 2026Review
- A discovery-based proteomic approach of epidermal growth factor and growth hormone-releasing peptide-6 in a model of acute ischemic stroke.Pharmacological reports : PR · 2026Article
- Article
- CD11c+ CD8 T cells cause IFN-γ-dependent autoimmune neuroinflammation that is restrained by PD-1 signaling.JCI insight · 2026Article
- Brain-wide mapping of oligodendrocyte organization, oligodendrogenesis, and myelin injury.Cell · 2026Article
- The glia-immune network: Astrocytes and oligodendrocytes as microglial co-ordinators in health and disease.The Journal of physiology · 2026Review
- Integrative behavioral, histological, and proteomics profiling identifies cerebellar drivers of motor dysfunction in a rat model of hepatic encephalopathy.Metabolic brain disease · 2025Article
- Single-nucleus transcriptomic profiling reveals temporal dynamics of neuroinflammation and myelin repair after intracerebral haemorrhage.Clinical and translational medicine · 2025Article
- Acute kidney injury disrupts cardiac remodeling via SerpinA3N.bioRxiv : the preprint server for biology · 2025Article
- A paradigm shift of SERPINA3N in neurobehavioral development and brain injury.bioRxiv : the preprint server for biology · 2025Article
- Astrocytic RIPK3 exerts protective anti-inflammatory activity in mice with viral encephalitis by transcriptional induction of serpins.Science signaling · 2025Article
- Oligodendrocytes in Alzheimer's disease pathophysiology.Nature neuroscience · 2025Review
- Manganese exposure induces parkinsonism-like symptoms by Serpina3n-TFEB-v/p-ATPase signaling mediated lysosomal dysfunction.Cell biology and toxicology · 2025Article
- Spatiotemporal transcriptomic map of glial cell response in a mouse model of acute brain ischemia.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Serine protease inhibitor, SerpinA3n, regulates cardiac remodelling after myocardial infarction.Cardiovascular research · 2024Article
- Granzyme serine proteases in inflammation and rheumatic diseases.Nature reviews. Rheumatology · 2024Review
- Regulation of CNS pathology by Serpina3n/SERPINA3: The knowns and the puzzles.Neuropathology and applied neurobiology · 2024Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultiple sclerosis (MS) is an autoimmune inflammatory and neurodegenerative disease of the central nervous system (CNS). It is widely accepted that inflammatory cells play major roles in the pathogenesis of MS, possibly through the use of serine protease granzyme B (GrB) secreted from the granules of cytotoxic T cells. We have previously identified GrB as a mediator of axonal injury and neuronal death. In this study, our goal was to evaluate the effect of GrB inhibition in the human system in vitro, and in vivo in EAE using the newly isolated GrB-inhibitor serpina3n.
methodsWe used a well-established in vitro model of neuroinflammation characterized by a co-culture system between human fetal neurons and lymphocytes. In vivo, we induced EAE in 10- to 12-week-old female C57/BL6 mice and treated them intravenously with serpina3n.
resultsIn the in vitro co-culture system, pre-treatment of lymphocytes with serpina3n prevented neuronal killing and cleavage of the cytoskeletal protein alpha-tubulin, a known substrate for GrB. Moreover, in EAE, 50 μg serpina3n substantially reduced the severity of the disease. This dose was administered intravenously twice at days 7 and 20 post EAE induction. serpina3n treatment reduced axonal and neuronal injury compared to the vehicle-treated control group and maintained the integrity of myelin. Interestingly, serpina3n treatment did not seem to reduce the infiltration of immune cells (CD4(+) and CD8(+) T cells) into the CNS.
conclusionOur data suggest further studies on serpina3n as a potentially novel therapeutic strategy for the treatment of inflammatory-mediated neurodegenerative diseases such as MS.
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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.