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Oxidative stress-dependent MMP-13 activity underlies glucose neurotoxicity

Ashley L Waldron1, Patricia A Schroder1, Kelly L Bourgon1

  • 1Davis Center for Regenerative Biology and Medicine, MDI Biological Laboratory, Kathryn W. Davis Building 227, Old Bar Harbor Road, Salisbury Cove, ME 04672, USA.

Journal of Diabetes and Its Complications
|January 8, 2018
PubMed
Abstract

Insights

Diabetic neuropathy involves sensory axon degeneration. This study shows reactive oxygen species (ROS) and MMP-13 drive this degeneration, and inhibiting MMP-13 may treat diabetic neuropathy.

Area of Science:

  • Neuroscience
  • Metabolic Disorders
  • Cell Biology

Background:

  • Diabetic neuropathy is a complication characterized by sensory axon degeneration.
  • The underlying mechanisms are unclear, but reactive oxygen species (ROS) are implicated.
  • This study investigates the roles of ROS and MMP-13 in glucose-induced axon degeneration.

Purpose of the Study:

  • To assess the role of ROS and MMP-13 in glucose-induced sensory axon degeneration.
  • To evaluate the potential of MMP-13 inhibition as a therapeutic strategy for diabetic neuropathy.

Main Methods:

  • Utilized zebrafish and mice models to study glucose-induced metabolic changes and axon degeneration.
  • Employed qPCR, live imaging, and specific fluorescent probes to analyze ROS and NF-κB activation.
  • Tested the efficacy of antioxidant treatment and MMP-13 inhibitors (DB04760, CL-82198) in preventing or reversing neuropathy.

Main Results:

  • Glucose treatment in zebrafish mimicked diabetic metabolic changes and induced sensory axon degeneration.
  • Degeneration was mediated by ROS-induced MMP-13, and was prevented by antioxidant or MMP-13 inhibition.
  • MMP-13 inhibition reversed neuropathy in both zebrafish and diabetic mice models.

Conclusions:

  • Zebrafish serve as a viable model for studying glucose-induced neurotoxicity.
  • MMP-13 inhibition shows promise as a therapeutic approach for human diabetic neuropathy, based on findings in zebrafish and mice.
Keywords:
EpidermisGlucoseMMP-13MiceNeuropathyROS

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