ArticleScientific reports2019
Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- Neuronal alkaline phosphatase promotes the spread of Tau-induced pathology, and its blockade prevents neurodegeneration and memory loss.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Article
- Exploring the impact of coffee consumption and caffeine intake on cognitive performance in older adults: a comprehensive analysis using NHANES data and gene correlation analysis.Nutrition journal · 2025Article
- Article
- Construction and Validation of a Nomogram Model for Predicting the Risk of Neonatal Sepsis Complicated by Purulent Meningitis.Journal of inflammation research · 2025Article
- recAP administration ameliorates sepsis outcomes through modulation of gut and liver inflammation.Biochemical and biophysical research communications · 2024Article
- Efficacy of Alkaline Phosphatase in Critically Ill Patients with COVID-19: A Multicentre Investigator-Initiated Double-Blind Randomised Placebo-Controlled Trial.Biomedicines · 2024Article
- Impact of alkaline phosphatase on clinical outcomes in patients with ischemic stroke: a nationwide registry analysis.Frontiers in neurology · 2024Article
- Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation.Biomedicines · 2022Article
- Alkaline Phosphatase: An Old Friend as Treatment Target for Cardiovascular and Mineral Bone Disorders in Chronic Kidney Disease.Nutrients · 2022Review
- TNAP as a therapeutic target for cardiovascular calcification: a discussion of its pleiotropic functions in the body.Cardiovascular research · 2022Review
- Insight Into Regulatory T Cells in Sepsis-Associated Encephalopathy.Frontiers in neurology · 2022Review
- Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?Frontiers in immunology · 2022Review
- The Physiological and Pathological Role of Tissue Nonspecific Alkaline Phosphatase beyond Mineralization.Biomolecules · 2021Review
- Tissue-Nonspecific Alkaline Phosphatase (TNAP) as the Enzyme Involved in the Degradation of Nucleotide Analogues in the Ligand Docking and Molecular Dynamics Approaches.Biomolecules · 2021Article
- Tissue-Nonspecific Alkaline Phosphatase in Central Nervous System Health and Disease: A Focus on Brain Microvascular Endothelial Cells.International journal of molecular sciences · 2021Review
- Disruption of metabolic, sleep, and sensorimotor functional outcomes in a female transgenic mouse model of Alzheimer's disease.Behavioural brain research · 2021Article
- A novel role for tissue-nonspecific alkaline phosphatase at the blood-brain barrier during sepsis.Neural regeneration research · 2021Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitous enzyme present in many cells and tissues, including the central nervous system. Yet its functions at the brain-immune axis remain unclear. The goal of this study was to use a novel small molecular inhibitor of TNAP, SBI-425, to interrogate the function of TNAP in neuroimmune disorders. Following intraperitoneal (IP) administration of SBI-425, mass spectrometry analysis revealed that the SBI-425 does not cross the blood-brain barrier (BBB) in healthy mice. To elucidate the role of TNAP at the brain-immune axis, mice were subjected to experimental sepsis and received either vehicle or SBI-425 (25 mg/kg, IP) daily for 7 days. While SBI-425 administration did not affect clinical severity outcomes, we found that SBI-425 administration suppressed CD4 + Foxp3+ CD25- and CD8 + Foxp3+ CD25- splenocyte T-cell populations compared to controls. Further evaluation of SBI-425's effects in the brain revealed that TNAP activity was suppressed in the brain parenchyma of SBI-425-treated mice compared to controls. When primary brain endothelial cells were treated with a proinflammatory stimulus the addition of SBI-425 treatment potentiated the loss of barrier function in BBB endothelial cells. To further demonstrate a protective role for TNAP at endothelial barriers within this axis, transgenic mice with a conditional overexpression of TNAP were subjected to experimental sepsis and found to have increased survival and decreased clinical severity scores compared to controls. Taken together, these results demonstrate a novel role for TNAP activity in shaping the dynamic interactions within the brain-immune axis.
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