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Published on: May 2, 2025

Receptor for advanced glycation end products activation injures primary sensory neurons via oxidative stress

Andrea M Vincent1, Lorena Perrone, Kelli A Sullivan

  • 1Department of Neurology, Room 5017 BSRB, University of Michigan, 109 Zina Pitcher Place, Ann Arbor, Michigan 48109, USA. andreav@umich.edu

Endocrinology
|November 11, 2006
PubMed

Insights

The receptor for advanced glycation end products (RAGE) is present in nerve cells and contributes to diabetic neuropathy by increasing oxidative stress. Therapies targeting RAGE or oxidative stress may prevent nerve damage in diabetes.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Molecular Biology

Background:

  • The receptor for advanced glycation end products (RAGE) is implicated in diabetic vascular and renal complications via oxidative stress pathways.
  • Limited research exists on RAGE expression and its role in diabetic neuropathy, a common complication of diabetes.

Purpose of the Study:

  • To investigate the presence and function of RAGE in dorsal root ganglia neurons.
  • To determine if RAGE activation in neurons contributes to oxidative stress and cellular injury relevant to diabetic neuropathy.

Main Methods:

  • Demonstrated functional RAGE expression in dorsal root ganglia neurons.
  • Exposed neurons to the RAGE ligand S100 to assess downstream signaling, oxidative stress, and cellular injury.
  • Evaluated the effect of the antioxidant alpha-lipoic acid on RAGE-mediated events.

Main Results:

  • Dorsal root ganglia neurons express functional RAGE and exhibit downstream signaling, oxidative stress, and cellular injury upon S100 stimulation.
  • RAGE activation led to increased reactive oxygen species, caspase-3 activation, and DNA degradation.
  • Alpha-lipoic acid treatment effectively prevented these RAGE-induced cellular damages.

Conclusions:

  • RAGE signaling in neurons contributes to oxidative stress and cellular injury, suggesting a role in diabetic neuropathy development.
  • Therapeutic strategies targeting RAGE ligands, RAGE signaling blockade, or oxidative stress prevention show promise for treating diabetic neuropathy.

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