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Targeting Inflammation Driven by HMGB1.

Huan Yang1, Haichao Wang2, Ulf Andersson3

  • 1Bioelectronic Medicine, Feinstein Institutes for Medical Research, Manhasset, NY, United States.

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|April 9, 2020
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Summary
This summary is machine-generated.

High mobility group box 1 (HMGB1) acts as an alarm protein, triggering innate immunity. HMGB1-specific inhibitors offer a new therapeutic strategy for inflammatory diseases by targeting its receptors.

Keywords:
HMGB1RAGETLR4danger signaldrug targetinflammation

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • High mobility group box 1 (HMGB1) is a nuclear protein with crucial extracellular functions.
  • Extracellular HMGB1 acts as a potent alarmin, activating innate immunity via TLR4 and RAGE receptors.
  • HMGB1 is recognized as a damage-associated molecular pattern molecule (DAMP).

Purpose of the Study:

  • To review the role of HMGB1 in inflammation.
  • To highlight HMGB1 as a therapeutic target in inflammatory diseases.
  • To discuss novel HMGB1-specific inhibitors.

Main Methods:

  • Literature review focusing on HMGB1's role in innate immunity and inflammation.
  • Analysis of HMGB1 interactions with TLR4 and RAGE.
  • Discussion of therapeutic strategies involving HMGB1 antagonists and inhibitors.

Main Results:

  • Disulfide HMGB1 binds to MD-2 within the TLR4 complex, distinct from LPS binding.
  • Therapeutic strategies include interrupting HMGB1/TLR4 activation and blocking RAGE-mediated endocytosis.
  • HMGB1-specific inhibitors are emerging as promising treatments for inflammatory conditions.

Conclusions:

  • HMGB1 is a key mediator of inflammation and a viable therapeutic target.
  • Targeting HMGB1 offers specific approaches to modulate innate immune responses.
  • Development of HMGB1 inhibitors presents a significant advancement in treating inflammatory diseases.