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NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...

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Region-Specific NRF2 Signaling in HIV-Associated Neurocognitive Disorders: A Transcriptomic and Computational

Grazia Scuderi1, Serena Spampinato2, Michelino Di Rosa1

  • 1Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.

Genes
|February 27, 2026
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Summary
This summary is machine-generated.

The NRF2 antioxidant pathway is a coordinated network in the brain, but it is selectively activated in white matter during HIV encephalitis, suggesting targeted therapies for HIV-associated neurocognitive disorders.

Keywords:
HANDHIVneurodegenerationoxidative stress

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Oxidative stress significantly contributes to HIV-associated neurocognitive disorders (HANDs).
  • The regional organization and function of the NRF2 antioxidant pathway in the human brain are not fully understood.
  • Understanding NRF2 pathway dynamics is crucial for developing effective HAND treatments.

Purpose of the Study:

  • To characterize the architecture and baseline expression of the NRF2 pathway in the human brain.
  • To investigate transcriptional and coexpression remodeling of the NRF2 pathway across different stages of HAND.
  • To identify potential therapeutic targets within the NRF2 signaling network for HAND.

Main Methods:

  • Reconstructed the NRF2 signaling network using pathway data and protein-protein interaction analysis.
  • Assessed baseline NRF2 gene expression in the normal human cortex.
  • Performed transcriptomic profiling on postmortem brain samples from individuals with HAND, including differential expression and coexpression analyses across brain regions.

Main Results:

  • Observed low-to-medium baseline expression of NRF2-related genes in the normal cortex.
  • Found minimal NRF2 pathway modulation in the frontal cortex and basal ganglia in HAND.
  • Detected robust NRF2 transcriptional activation specifically in white matter during HIV encephalitis (HIVE).
  • Revealed a highly coordinated transcriptional organization of the NRF2 network across all analyzed brain regions in HAND samples.

Conclusions:

  • The NRF2 signaling pathway is maintained as a coordinated network in HAND.
  • Selective activation of NRF2 occurs in white matter during HIV encephalitis.
  • These findings highlight opportunities for region- and cell-type-specific therapeutic interventions for HAND.