ArticleJournal of neurovirology2003
The chemokine receptor CXCR4 regulates cell-cycle proteins in neurons.
Article in Journal of neurovirology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 66 citations in OpenAlex.
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- CXCL14 Maintains hESC Self-Renewal through Binding to IGF-1R and Activation of the IGF-1R Pathway.Cells · 2020Article
- Osteopontin and Integrin Mediated Modulation of Post-Synapses in HIV Envelope Glycoprotein Exposed Hippocampal Neurons.Brain sciences · 2020Article
- Transcriptome Analysis Reveals Distinct Responses to PhysiologicFrontiers in genetics · 2019Article
- Entanglement of CCR5 and Alzheimer's Disease.Frontiers in aging neuroscience · 2019Review
- CXCR4 involvement in neurodegenerative diseases.Translational psychiatry · 2018Article
- The Role of SDF-1/CXCR4/CXCR7 in Neuronal Regeneration after Cerebral Ischemia.Frontiers in neuroscience · 2017Review
- Progesterone modulates endothelial progenitor cell (EPC) viability through the CXCL12/CXCR4/PI3K/Akt signalling pathway.Cell proliferation · 2016Article
- A Novel Role of Proline Oxidase in HIV-1 Envelope Glycoprotein-induced Neuronal Autophagy.The Journal of biological chemistry · 2015Article
- Induction of Interleukin-1β by Human Immunodeficiency Virus-1 Viral Proteins Leads to Increased Levels of Neuronal Ferritin Heavy Chain, Synaptic Injury, and Deficits in Flexible Attention.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Mechanisms of HIV-1 Tat neurotoxicity via CDK5 translocation and hyper-activation: role in HIV-associated neurocognitive disorders.Current HIV research · 2015Review
- Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction.The Journal of clinical investigation · 2014Article
- Viral and cellular factors underlying neuropathogenesis in HIV associated neurocognitive disorders (HAND).AIDS research and therapy · 2014Review
- Functions of the chemokine receptor CXCR4 in the central nervous system and its regulation by μ-opioid receptors.International review of neurobiology · 2014Review
- CXCL12 signaling in the development of the nervous system.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2012Review
- Effects of opiates and HIV proteins on neurons: the role of ferritin heavy chain and a potential for synergism.Current HIV research · 2012Review
- G-protein-coupled receptors in adult neurogenesis.Pharmacological reviews · 2012Review
- Regulation of neuronal ferritin heavy chain, a new player in opiate-induced chemokine dysfunction.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2011Review
- Bilaminar co-culture of primary rat cortical neurons and glia.Journal of visualized experiments : JoVE · 2011Article
- Rescue of adult hippocampal neurogenesis in a mouse model of HIV neurologic disease.Neurobiology of disease · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Neurons express a variety of chemokine receptors that regulate neuronal signaling and survival, including CXCR4 and CCR5, the two major human immunodeficiency virus (HIV) coreceptors. However, the role of chemokine receptors in HIV neuropathology and neuroinflammatory disorders is still unclear. This study aims to determine whether chemokine receptors regulate the activity of cell-cycle proteins in neurons and evaluate the possibility that alterations of these proteins are involved in HIV neuropathogenesis. The authors studied the effect of the chemokine stromal cell-derived factor (SDF)-1alpha, the natural CXCR4 ligand, and an X4-using variant of gp120 on the activity of cell-cycle proteins involved in neuronal apoptosis and differentiation, such as Rb and E2F-1. Changes in expression, localization, and phosphorylation/activation of Rb and E2F-1 induced by SDF-1alpha (20 nM) gp120(IIIB) (200 pM) were analyzed in primary cultures of rat neurons and in a human cell line expressing recombinant CXCR4. The data indicate that changes in the nuclear and cytosolic levels of Rb--which result in the functional loss of this protein--are associated with apoptosis in hippocampal or cerebellar granule neurons and in cell lines. SDF-1alpha, which is able to rescue these neurons from apoptosis, induces a time-dependent increase of total Rb expression while decreasing the nuclear content of phosphorylated (Ser780/Ser795) Rb and the transcriptional activity of E2F-1. The HIV envelope protein gp120(IIIB) exerts opposite effects at the nuclear level. These data indicate that CXCR4 affects cell-cycle proteins in neurons and raise the possibility that chemokines may contribute to neuronal survival by repressing the activity of E2F-dependent apoptotic genes and maintaining neurons in a highly differentiated and quiescent state. This state may be altered during neuroinflammatory conditions and/or by HIV-derived proteins.
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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.