ArticleScientific reports2016
Smoothened Agonist Reduces Human Immunodeficiency Virus Type-1-Induced Blood-Brain Barrier Breakdown in Humanized Mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 51 citations in OpenAlex.
- Review
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- Hedgehog Signaling Functions in Spermatogenesis and Keeping Hemolymph-Testis Barrier Stability inInternational journal of molecular sciences · 2025Article
- Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.Cells · 2024Review
- Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS.NeuroImmune pharmacology and therapeutics · 2024Article
- Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.PNAS nexus · 2024Article
- HIV-Associated Neurocognitive Disorder: A Look into Cellular and Molecular Pathology.International journal of molecular sciences · 2024Review
- Initiation of combined antiretroviral therapy confers suboptimal beneficial effects on neurovascular function in people with HIV.Frontiers in neurology · 2023Article
- Review
- Understanding Abnormal SMO-SHH Signaling in Autism Spectrum Disorder: Potential Drug Target and Therapeutic Goals.Cellular and molecular neurobiology · 2022Review
- Human immunodeficiency virus-1 Tat exerts its neurotoxic effects by downregulating Sonic hedgehog signaling.Journal of neurovirology · 2022Article
- The Emerging Role of Hedgehog Signaling in Viral Infections.Frontiers in microbiology · 2022Review
- The hedgehog pathway suppresses neuropathogenesis in CD4 T cell-driven inflammation.Brain : a journal of neurology · 2021Article
- Meningitic Escherichia coli α-hemolysin aggravates blood-brain barrier disruption via targeting TGFβ1-triggered hedgehog signaling.Molecular brain · 2021Article
- Monocytes complexed to platelets differentiate into functionally deficient dendritic cells.Journal of leukocyte biology · 2021Article
- Systemic Pharmacological Smoothened Inhibition Reduces Lung T-Cell Infiltration and Ameliorates Th2 Inflammation in a Mouse Model of Allergic Airway Disease.Frontiers in immunology · 2021Article
- Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.PLoS biology · 2020Article
- Novel Mechanism of Microvesicle Regulation by the Antiviral Protein Tetherin During HIV Infection.Journal of the American Heart Association · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Human Immunodeficiency Virus type-1 (HIV)-associated neurocognitive disorder is characterized by recruitment of activated/infected leukocytes into the CNS via disrupted Blood Brain Barrier (BBB) that contributes to persistent neuro-inflammation. In this report, humanized NOD/scid-IL2Rγc(null) mice were used to establish that impaired Sonic hedgehog (Shh) signaling is associated with loss of BBB function and neurological damage, and that modulating Shh signaling can rescue these detrimental effects. Plasma viral load, p24 levels and CD4(+) T cells were measured as markers of productive HIV infection. These mice also showed impaired exclusion of Evans blue dye from the brain, increased plasma levels of S100B, an astrocytic protein, and down-regulation of tight junction proteins Occludin and Claudin5, collectively indicating BBB dysfunction. Further, brain tissue from HIV(+) mice indicated reduced synaptic density, neuronal atrophy, microglial activation, and astrocytosis. Importantly, reduced expression of Shh and Gli1 was also observed in these mice, demonstrating diminished Shh signaling. Administration of Shh mimetic, smoothened agonist (SAG) restored BBB integrity and also abated the neuropathology in infected mice. Together, our results suggest a neuroprotective role for Shh signaling in the context of HIV infection, underscoring the therapeutic potential of SAG in controlling HAND pathogenesis.
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