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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kruman, II; Nath, A; Maragos, WF; Chan, SL; Jones, M; Rangnekar, VM; Jakel, RJ; Mattson, MP

Published Date

  • July 1999

Published In

Volume / Issue

  • 155 / 1

Start / End Page

  • 39 - 46

PubMed ID

  • 10393834

Pubmed Central ID

  • PMC1866661

International Standard Serial Number (ISSN)

  • 0002-9440

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)65096-1


  • eng

Conference Location

  • United States