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Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy

Author

Listed:
  • Stephanie I. Shiers

    (The University of Texas at Dallas)

  • Khadijah Mazhar

    (The University of Texas at Dallas)

  • Andi Wangzhou

    (The University of Texas at Dallas)

  • Rainer Haberberger

    (The University of Adelaide)

  • Joseph B. Lesnak

    (The University of Texas at Dallas)

  • Nwasinachi A. Ezeji

    (The University of Texas at Dallas)

  • Ishwarya Sankaranarayanan

    (The University of Texas at Dallas)

  • Diana Tavares-Ferreira

    (The University of Texas at Dallas)

  • Anna Cervantes

    (Southwest Transplant Alliance)

  • Geoffrey Funk

    (Southwest Transplant Alliance)

  • Peter Horton

    (Southwest Transplant Alliance)

  • Erin Vines

    (Southwest Transplant Alliance)

  • Gregory Dussor

    (The University of Texas at Dallas)

  • Theodore J. Price

    (The University of Texas at Dallas)

Abstract

Nageotte nodules, first described in 1922 by Jean Nageotte, are clusters of non-neuronal cells that form after sensory neuron death. Despite their historical recognition, little is known about their molecular identity nor their involvement in neuropathies that involve neuronal loss like diabetic peripheral neuropathy (DPN). In this study, we molecularly characterize Nageotte nodules in dorsal root ganglia recovered from organ donors with DPN. Here we show that Nageotte nodules are abundant in DPN sensory ganglia and account for 25% of all neurons. Peripherin-and Nav1.7-positive dystrophic axons invade Nageotte nodules, forming small neuroma-like structures. Using histology and spatial sequencing, we demonstrate that Nageotte nodules are mainly composed of satellite glia and non-myelinating Schwann cells that express SPP1 and are intertwined with sprouting sensory axons originating from neighboring neurons. Our findings suggest that Nageotte nodules are an integral feature of dorsal root ganglion neurodegeneration, providing potential therapeutic targets for sensory neuron protection and pain management in DPN.

Suggested Citation

  • Stephanie I. Shiers & Khadijah Mazhar & Andi Wangzhou & Rainer Haberberger & Joseph B. Lesnak & Nwasinachi A. Ezeji & Ishwarya Sankaranarayanan & Diana Tavares-Ferreira & Anna Cervantes & Geoffrey Fun, 2025. "Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59538-z
    DOI: 10.1038/s41467-025-59538-z
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    References listed on IDEAS

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    1. Zhiyuan Liu & Dafei Wu & Weiwei Zhai & Liang Ma, 2023. "SONAR enables cell type deconvolution with spatially weighted Poisson-Gamma model for spatial transcriptomics," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
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