Evidence that Par-4 participates in the pathogenesis of HIV encephalitis

Inna I. Kruman, Avindra Nath, William F. Maragos, Sic L. Chan, Melina Jones, Vivek M. Rangnekar, Rebekah J. Jakel, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Progressive neuronal degeneration in brain regions involved in learning and memory processes is a common occurrence in patients infected with human immunodeficiency virus type 1 (HIV-1). We now report that levels of Par-4, a protein recently linked to neuronal apoptosis in Alzheimer's disease, are increased in neurons in hippocampus of human patients with HIV encephalitis and in monkeys infected with a chimeric strain of HIV-1 and simian immunodeficiency virus. Par-4 levels increased rapidly in cultured hippocampal neurons following exposure to the neurotoxic HIV-1 protein Tat, and treatment of the cultures with a Par-4 antisense oligonucleotide protected the neurons against Tat-induced apoptosis. Additional findings show that Par-4 participates at an early stage of Tat-induced neuronal apoptosis before caspase activation, oxidative stress, and mitochondrial dysfunction. Our data suggest that Par-4 may be a mediator of neuronal apoptosis in HIV encephalitis and that therapeutic approaches targeting the Par-4 apoptotic cascade may prove beneficial in preventing neuronal degeneration and associated dementia in patients infected with HIV-1.

Original languageEnglish
Pages (from-to)39-46
Number of pages8
JournalAmerican Journal of Pathology
Issue number1
StatePublished - Jul 1999

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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