Related Experiment Video

Updated: Sep 24, 2026

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
09:12

Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates

Published on: January 30, 2014

Proteasome blockers inhibit TNF-alpha release by lipopolysaccharide stimulated macrophages and microglia:

S M Fine1, S B Maggirwar, P R Elliott

  • 1Department of Medicine, University of Rochester Medical Center, NY 14642, USA. steven_fine@urmc.rochester.edu

Journal of Neuroimmunology
|May 6, 1999
PubMed

Insights

Proteasome inhibitors block tumor necrosis factor alpha (TNF-alpha) release in HIV-1 infected brain cells. This NF-kappaB inhibition may offer a new strategy for treating HIV-1 dementia.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • HIV-1 infection in the central nervous system can lead to severe neurological conditions.
  • Only microglial cells and brain macrophages are productively infected by HIV-1.
  • Disease pathogenesis is thought to be mediated by substances secreted from infected cells, such as TNF-alpha.

Purpose of the Study:

  • To investigate the role of NF-kappaB activation in TNF-alpha production during HIV-1 infection.
  • To evaluate the efficacy of proteasome inhibitors in blocking TNF-alpha release.
  • To explore a novel therapeutic strategy for HIV-1-associated dementia.

Main Methods:

  • Primary human fetal microglia (PHFM) and monocyte-derived macrophages were treated with proteasome inhibitors MG132 and ALLN.
  • Lipopolysaccharide (LPS) or TNF-alpha was used to stimulate TNF-alpha release.
  • Electrophoretic mobility shift assay (EMSA) was performed to analyze NF-kappaB activation.

Main Results:

  • Proteasome inhibitors MG132 and ALLN effectively blocked TNF-alpha release stimulated by LPS or TNF-alpha.
  • LPS stimulation activated the p50/p65 heterodimer of NF-kappaB in microglia.
  • MG132 inhibited LPS-induced NF-kappaB activation in microglia.

Conclusions:

  • Inhibition of NF-kappaB activation in microglia reduces TNF-alpha production in vitro.
  • Targeting NF-kappaB activation represents a potential therapeutic approach for HIV-1 dementia.

More Related Videos

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia07:18

Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia

Published on: November 9, 2018

Isolation, Transfection, and Culture of Primary Human Monocytes09:13

Isolation, Transfection, and Culture of Primary Human Monocytes

Published on: December 16, 2019

Related Concept Videos

The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...