ArticleScientific reports2017
Sonic Hedgehog mimetic prevents leukocyte infiltration into the CNS during acute HIV infection.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- 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
- Meningitic Escherichia coli α-hemolysin aggravates blood-brain barrier disruption via targeting TGFβ1-triggered hedgehog signaling.Molecular brain · 2021Article
- HIV-1 and drug abuse comorbidity: Lessons learned from the animal models of NeuroHIV.Neuroscience letters · 2021Review
- Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms.Fluids and barriers of the CNS · 2020Review
- Sonic Hedgehog signaling limits atopic dermatitis via Gli2-driven immune regulation.The Journal of clinical investigation · 2019Article
- Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance.International journal of molecular sciences · 2019Review
- Astrocyte-Derived Paracrine Signals: Relevance for Neurogenic Niche Regulation and Blood-Brain Barrier Integrity.Frontiers in pharmacology · 2019Review
- Antidepressant, anti-inflammatory, and antioxidant effects of electroacupuncture through sonic hedgehog-signaling pathway in a rat model of poststroke depression.Neuropsychiatric disease and treatment · 2019Article
- Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond.International journal of molecular sciences · 2018Review
- Human Immune System Mice for the Study of Human Immunodeficiency Virus-Type 1 Infection of the Central Nervous System.Frontiers in immunology · 2018Review
- The Hedgehog Signaling Pathway Emerges as a Pathogenic Target.Journal of developmental biology · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Infiltration of infected leukocytes culminates in establishment of a brain niche for Human Immunodeficiency Virus (HIV) during acute phase of infection, initiating an ongoing cascade of persistent viral replication and inflammation, that causes irreversible neuronal injury and HIV associated neurocognitive disease (HAND). In this study, humanized mice were treated with Smoothened Agonist (SAG), a Sonic Hedgehog (Shh) mimetic in order to fortify blood brain barrier (BBB) and dampen leukocyte extravasation into CNS during AHI. Results indicate that SAG treatment reduced viral burden in the CNS immediately after HIV transmission, but also conferred extended neuroprotection via increased BBB integrity (elevated levels of tight-junction protein, Claudin 5, and reduced S100B levels in periphery). These mice also showed healthier neurons with thick, uniform dendrites and reduced numbers of activated astrocytes. Additional in vitro experiments suggested SAG treatment was not associated with the establishment or reversal of latency in the target cells. Altogether, these findings validate neuroprotective role of Shh signaling and highlight the therapeutic potential of Shh mimetics against CNS complications associated with HIV infection. Further our results strongly demonstrate that pharmacological interventions to reduce leukocyte mobilization during early HIV infection, can provide prolonged neuroprotection, which might significantly delay the onset of HAND.
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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.