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 journalArticle

Abstract

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 (US)
Pages (from-to)39-46
Number of pages8
JournalAmerican Journal of Pathology
Volume155
Issue number1
StatePublished - Jul 1999
Externally publishedYes

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Encephalitis
HIV-1
HIV
Apoptosis
Neurons
Human Immunodeficiency Virus Proteins
Simian Immunodeficiency Virus
Antisense Oligonucleotides
Caspases
Haplorhini
Dementia
Hippocampus
Alzheimer Disease
Oxidative Stress
Learning
Brain
Therapeutics
Proteins

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Kruman, I. I., Nath, A., Maragos, W. F., Chan, S. L., Jones, M., Rangnekar, V. M., ... Mattson, M. P. (1999). Evidence that Par-4 participates in the pathogenesis of HIV encephalitis. American Journal of Pathology, 155(1), 39-46.

Evidence that Par-4 participates in the pathogenesis of HIV encephalitis. / Kruman, Inna I.; Nath, Avindra; Maragos, William F.; Chan, Sic L.; Jones, Melina; Rangnekar, Vivek M.; Jakel, Rebekah J.; Mattson, Mark P.

In: American Journal of Pathology, Vol. 155, No. 1, 07.1999, p. 39-46.

Research output: Contribution to journalArticle

Kruman, II, Nath, A, Maragos, WF, Chan, SL, Jones, M, Rangnekar, VM, Jakel, RJ & Mattson, MP 1999, 'Evidence that Par-4 participates in the pathogenesis of HIV encephalitis', American Journal of Pathology, vol. 155, no. 1, pp. 39-46.
Kruman II, Nath A, Maragos WF, Chan SL, Jones M, Rangnekar VM et al. Evidence that Par-4 participates in the pathogenesis of HIV encephalitis. American Journal of Pathology. 1999 Jul;155(1):39-46.
Kruman, Inna I. ; Nath, Avindra ; Maragos, William F. ; Chan, Sic L. ; Jones, Melina ; Rangnekar, Vivek M. ; Jakel, Rebekah J. ; Mattson, Mark P. / Evidence that Par-4 participates in the pathogenesis of HIV encephalitis. In: American Journal of Pathology. 1999 ; Vol. 155, No. 1. pp. 39-46.
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