The Tat antagonist neomycin B hexa-arginine conjugate inhibits gp-120-induced death of human neuroblastoma cells

Maria Valeria Catani, Maria Tiziana Corasaniti, Marco Ranalli, Diana Amantea, Alexander Litovchick, Aviva Lapidot, Gerry Melino

Research output: Contribution to journalArticlepeer-review

Abstract

Several patients with acquired immunodeficiency syndrome (AIDS) develop neurological complications, which are referred to as human immunodeficiency virus (HIV)-associated dementia (HAD). The HIV-1 coat glycoprotein gp-120 has been proposed as the major etiologic agent for neuronal loss reported postmortem in the brain of AIDS patients. Chemokine receptors may play a role in gp-120-triggered neurotoxicity, both in vitro and in vivo, thus being an intriguing target for developing therapeutic strategies aimed to prevent or reduce neuronal damage occurring during HIV infection. We have previously shown that human CHP100 neuroblastoma cells express CXCR4 and CCR5 chemokine receptors and that interaction between gp-120 and these receptors contributes to cytotoxicity elicited by the protein. Here, we examined the neuroprotective potential of neomycin B hexa-arginine conjugate (NeoR), a recently synthesized compound with anti-HIV activity. We found that gp-120-triggered death is significantly reduced by NeoR, and this protective effect seems related to the ability of NeoR to interact with CXCR4 receptors. The ability of NeoR to cross the blood-brain barrier, as demonstrated in mice by systemic administration of the fluorescein conjugate drug, makes this compound a powerful and attractive therapeutic agent.

Original languageEnglish
Pages (from-to)1237-1245
Number of pages9
JournalJournal of Neurochemistry
Volume84
Issue number6
DOIs
Publication statusPublished - Mar 2003

Keywords

  • Aminoglycoside-arginine conjugate
  • Blood-brain barrier
  • Cell death
  • Chemokine receptors
  • Gp-120
  • Neomycin B-hexa-arginine conjugate

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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