ArticleProceedings of the National Academy of Sciences of the United States of America2006
Proteolytic processing of SDF-1alpha reveals a change in receptor specificity mediating HIV-associated neurodegeneration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 97 citations in OpenAlex.
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- Advances in the Experimental Models of HIV-Associated Neurological Disorders.Current HIV/AIDS reports · 2021Review
- Co-receptor signaling in the pathogenesis of neuroHIV.Retrovirology · 2021Review
- Mechanisms of neuronal dysfunction in HIV-associated neurocognitive disorders.Cellular and molecular life sciences : CMLS · 2021Review
- Differential activity and selectivity of N-terminal modified CXCL12 chemokines at the CXCR4 and ACKR3 receptors.Journal of leukocyte biology · 2020Article
- SerpinA3N deficiency deteriorates impairments of learning and memory in mice following hippocampal stab injury.Cell death discovery · 2020Article
- Matrix metalloproteinases in the CNS: interferons get nervous.Cellular and molecular life sciences : CMLS · 2019Review
- What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands.Pharmacology & therapeutics · 2019Review
- C-terminal truncation of IFN-γ inhibits proinflammatory macrophage responses and is deficient in autoimmune disease.Nature communications · 2018Article
- HIV-associated synaptic degeneration.Molecular brain · 2017Review
- Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- CXCL12-induced neurotoxicity critically depends on NMDA receptor-gated and L-type CaJournal of neuroinflammation · 2016Article
- HIV-1, methamphetamine and astrocytes at neuroinflammatory Crossroads.Frontiers in microbiology · 2015Review
- Progesterone protects normative anxiety-like responding among ovariectomized female mice that conditionally express the HIV-1 regulatory protein, Tat, in the CNS.Hormones and behavior · 2014Article
- Neuronal ferritin heavy chain and drug abuse affect HIV-associated cognitive dysfunction.The Journal of clinical investigation · 2014Article
- Functions of the chemokine receptor CXCR4 in the central nervous system and its regulation by μ-opioid receptors.International review of neurobiology · 2014Review
- Proteolytic processing of SDF-1α by matrix metalloproteinase-2 impairs CXCR4 signaling and reduces neural progenitor cell migration.Protein & cell · 2012Article
- Effects of opiates and HIV proteins on neurons: the role of ferritin heavy chain and a potential for synergism.Current HIV research · 2012Review
- Delineating HIV-associated neurocognitive disorders using transgenic models: the neuropathogenic actions of Vpr.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2012Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Proteolytic cleavage of constitutively expressed proteins can generate peptides with novel bioactive properties. Matrix metalloproteinase (MMP)-2 cleaves the 4 amino-terminal residues of the chemokine, stromal cell-derived factor (SDF)-1alpha, yielding a highly neurotoxic molecule, SDF(5-67), which fails to bind to its cognate receptor, CXCR4. Herein, we detected SDF(5-67) in brain monocytoid cells of HIV-infected persons, particularly in those with HIV-associated dementia. SDF(5-67) activated cell type-specific expression of proinflammatory genes including IL-1beta, TNFalpha, indoleamine 2',3'-dioxygenase (IDO), and IL-10 in both astrocytic and monocytoid cells (P < 0.05). Unlike SDF-1alpha, SDF(5-67) caused neuronal membrane perturbations with ensuing neurotoxicity and apoptosis (P < 0.05) through engagement of an inducible receptor. CXCR3 antagonists and siRNA-mediated knockdown of CXCR3 inhibited SDF(5-67)-stimulated neurophysiological changes, neuronal death, and neuroimmune activation (P < 0.05). Moreover SDF(5-67) bound directly to CXCR3 in a competitive manner, mediated by its amino terminus. In vivo neuroinflammation, neuronal loss, and neurobehavioral abnormalities caused by SDF(5-67) (P < 0.05) were prevented by a CXCR3 antagonist. These studies reveal additive neuropathogenic properties exerted by a proteolytically cleaved chemokine as consequences of a change in receptor specificity, culminating in neurodegeneration.
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