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Related Concept Videos

Inflammatory Response01:28

Inflammatory Response

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An inflammatory response is a localized, nonspecific immune reaction that occurs when a tissue is injured. It is characterized by redness, swelling, heat, and pain, which are commonly called the cardinal signs and symptoms of inflammation. Inflammation can sometimes result in a loss of function.
Inflammation can be triggered by various stimuli, such as impact, abrasion, chemical irritation, infections, and extreme hot or cold temperatures. These can damage cells and connective tissue fibers,...
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Increased Recovery Time and Decreased LPS Administration to Study the Vagus Nerve Stimulation Mechanisms in Limited Inflammatory Responses
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Modulating the RAGE-Induced Inflammatory Response: Peptoids as RAGE Antagonists.

Mihyun Lim Waugh1, Lauren M Wolf1, James P Turner2

  • 1Biomedical Engineering Program, University of South Carolina, 3A46 Swearingen Engineering Center, Columbia, SC 29208, USA.

Chembiochem : a European Journal of Chemical Biology
|September 7, 2023
PubMed
Summary

New peptoids show promise in treating Alzheimer's disease (AD) by targeting the receptor for advanced glycation end-products (RAGE). These compounds reduce neuroinflammation, offering a potential therapeutic strategy for AD and other neurodegenerative conditions.

Keywords:
Alzheimer's diseaseRAGEamyloid-β proteinneuroinflammationpeptoid

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Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Alzheimer's disease (AD) pathology involves amyloid-β plaques and tau tangles, with chronic neuroinflammation playing a significant role.
  • The receptor for advanced glycation end-products (RAGE) is upregulated in AD, mediating inflammatory responses through its ligands like amyloid-β.
  • Current AD therapeutics do not target RAGE-mediated neuroinflammation, highlighting an unmet clinical need.

Purpose of the Study:

  • To design and evaluate peptoids as novel RAGE antagonists for treating AD-associated neuroinflammation.
  • To investigate the binding affinity of designed peptoids to RAGE.
  • To assess the efficacy of peptoids in attenuating RAGE-mediated inflammatory responses.

Main Methods:

  • Peptoids were designed to mimic amyloid-β and inhibit RAGE activation.
  • Binding affinity of peptoids JPT1 and JPT1a to RAGE was determined.
  • Lipopolysaccharide-induced pro-inflammatory cytokine production and RAGE cell surface expression were measured in the presence of peptoids.

Main Results:

  • Peptoids JPT1 and JPT1a exhibited nanomolar binding affinity to RAGE.
  • These peptoids effectively attenuated lipopolysaccharide-induced pro-inflammatory cytokine release.
  • The peptoids also reduced the upregulation of RAGE cell surface expression.

Conclusions:

  • Peptoid-based RAGE antagonists demonstrate potential as a therapeutic strategy for Alzheimer's disease.
  • This approach may be beneficial in combating neuroinflammation in AD and other neurodegenerative diseases.
  • Peptoids offer advantages such as low toxicity and blood-brain barrier permeability.