Mixed lineage kinase 3 mediates gp120IIIB-induced neurotoxicity

Amos Bodner, Anna C. Maroney, James P. Finn, Ghanashyam Ghadge, Raymond Roos, Richard J. Miller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Overexpression of gp120, the major coat protein of the HIV-1 virus, in central glial cells, or treatment of neurons with gp120 in culture, produces apoptotic neuronal death. Here we demonstrate that CEP-1347 (KT7515), an inhibitor of mixed lineage kinase 3 (MLK3), an upstream activator of JNK, inhibits gp120IIIB-induced apoptosis of hippocampal neurons. Furthermore, expression of wild type MLK3 in hippocampal pyramidal neurons enhanced gp120IIIB-induced neurotoxicity, whereas expression of a dominant negative MLK3 protected neurons from the toxic effects of the glycoprotein. These results indicate a role for MLK3 signaling in gp120IIIB-induced neuronal death, and suggest potential clinical utility of CEP-1347 in inhibiting the progression of AIDS dementia.

Original languageEnglish (US)
Pages (from-to)1424-1434
Number of pages11
JournalJournal of neurochemistry
Volume82
Issue number6
DOIs
StatePublished - Sep 2002

Keywords

  • AIDS
  • Apoptosis
  • CEP-1347
  • HIV-1 gp120IIIB
  • MLK3
  • Neuron

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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