ArticleCellular & molecular immunology2021
Targeting the CD146/Galectin-9 axis protects the integrity of the blood-brain barrier in experimental cerebral malaria.
Article in Cellular & molecular immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Splenic macrophage-B cell axis drives systemic autoimmune-like pathology in Cerebral Malaria.Nature communications · 2026Article
- Galectin-9 activates microglial asparagine endopeptidase and promotes α-synuclein pathology in Parkinson's disease.Cell death and differentiation · 2026Article
- FA-2-b-β modulates HMGB1/NF-κB/NLRP3 signaling to alleviate neuroinflammation in Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2026Article
- Galectin-9-An Emerging Glyco-Immune Checkpoint Target for Cancer Therapy.International journal of molecular sciences · 2025Review
- NR2F6 as a Disease Driver and Candidate Therapeutic Target in Experimental Cerebral Malaria.Cells · 2025Article
- The blood-brain barrier: a help and a hindrance.Brain : a journal of neurology · 2025Review
- Article
- A rat model establishment of bronchopulmonary dysplasia-related lung & brain injury within 28 days after birth.BMC neuroscience · 2024Article
- CD146, a therapeutic target involved in cell plasticity.Science China. Life sciences · 2024Review
- CD8CNS neuroscience & therapeutics · 2024Article
- Galectins in Protozoan Parasitic Diseases: Potential Applications in Diagnostics and Therapeutics.Cells · 2023Review
- A subpopulation of CD146Cellular & molecular immunology · 2023Article
- Interplay Between the Immune and Nervous Cognitive Systems in Homeostasis and in Malaria.International journal of biological sciences · 2023Review
- Galectin functions in cancer-associated inflammation and thrombosis.Frontiers in cardiovascular medicine · 2023Review
- CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases.Science China. Life sciences · 2022Article
- CD146 Associates with Gp130 to Control a Macrophage Pro-inflammatory Program That Regulates the Metabolic Response to Obesity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Knockdown of CD146 promotes endothelial-to-mesenchymal transition via Wnt/β-catenin pathway.PloS one · 2022Article
- MeningiticFrontiers in cellular neuroscience · 2022Article
- Structure basis for AA98 inhibition on the activation of endothelial cells mediated by CD146.iScience · 2021Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cerebral malaria (CM) is a life-threatening diffuse encephalopathy caused by Plasmodium falciparum, in which the destruction of the blood-brain barrier (BBB) is the main cause of death. However, increasing evidence has shown that antimalarial drugs, the current treatment for CM, do little to protect against CM-induced BBB damage. Therefore, a means to alleviate BBB dysfunction would be a promising adjuvant therapy for CM. The adhesion molecule CD146 has been reported to be expressed in both endothelial cells and proinflammatory immune cells and mediates neuroinflammation. Here, we demonstrate that CD146 expressed on BBB endothelial cells but not immune cells is a novel therapeutic target in a mouse model of experimental cerebral malaria (eCM). Endothelial CD146 is upregulated during eCM development and facilitates the sequestration of infected red blood cells (RBCs) and/or proinflammatory lymphocytes in CNS blood vessels, thereby promoting the disruption of BBB integrity. Mechanistic studies showed that the interaction of CD146 and Galectin-9 contributes to the aggregation of infected RBCs and lymphocytes. Deletion of endothelial CD146 or treatment with the anti-CD146 antibody AA98 prevents severe signs of eCM, such as limb paralysis, brain vascular leakage, and death. In addition, AA98 combined with the antiparasitic drug artemether improved the cognition and memory of mice with eCM. Taken together, our findings suggest that endothelial CD146 is a novel and promising target in combination with antiparasitic drugs for future CM therapies.
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Registered trials
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.