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Advanced Glycation End-Products Sensitize Human Sensory-Like Neuron Cells to Capsaicin-Induced Calcium Influx
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Glycation of the high affinity NGF-receptor and RAGE leads to reduced ligand affinity

Dorit Bennmann1, Christoph Kannicht2, Claudine Fisseau2

  • 1Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Hollystr. 1, D-06114 Halle (Saale), Germany.

Mechanisms of Ageing and Development
|July 28, 2015
PubMed

Insights

Glycation, a process linked to aging, impairs protein function. This study shows glycation reduces the binding affinity of the NGF receptor TrkA and the AGE receptor RAGE, impacting cellular processes.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Neuroscience

Background:

  • Advanced Glycation End-products (AGEs) result from protein glycation, a non-enzymatic reaction.
  • Glycation leads to less functional proteins, inflammation, and neurodegeneration.
  • The high-affinity NGF receptor TrkA and the AGE receptor RAGE are implicated in aging and neurodegeneration.

Purpose of the Study:

  • To investigate the impact of glycation on the binding affinities of TrkA and RAGE.
  • To establish a glycation procedure using Surface Plasmon Resonance (SPR).
  • To assess the functional consequences of TrkA glycation on NGF-dependent neurite outgrowth.

Main Methods:

  • Surface Plasmon Resonance (SPR) was used to quantify binding affinities.
  • A glycation procedure was optimized and established using SPR.
  • Neurite outgrowth in PC12 cells was measured to assess functional changes.

Main Results:

  • Glycation reduced TrkA's affinity for NGF by threefold.
  • Glycated TrkA led to decreased NGF-dependent neurite outgrowth in PC12 cells.
  • Glycation reduced RAGE's binding affinity for AGEs by tenfold.

Conclusions:

  • Glycation significantly impairs the function of key receptors involved in neuronal signaling and aging.
  • These findings highlight the detrimental effects of glycation on TrkA and RAGE, with implications for neurodegenerative diseases.
  • The study provides a method for assessing glycation effects on receptor-ligand interactions.
Keywords:
Advanced glycation endproducts (AGEs)Binding affinityGlycationNeuronal plasticityRAGETrkA

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