Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy
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 dia...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41467-025-59538-z |
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| author | Stephanie I. Shiers Khadijah Mazhar Andi Wangzhou Rainer Haberberger Joseph B. Lesnak Nwasinachi A. Ezeji Ishwarya Sankaranarayanan Diana Tavares-Ferreira Anna Cervantes Geoffrey Funk Peter Horton Erin Vines Gregory Dussor Theodore J. Price |
| author_facet | Stephanie I. Shiers Khadijah Mazhar Andi Wangzhou Rainer Haberberger Joseph B. Lesnak Nwasinachi A. Ezeji Ishwarya Sankaranarayanan Diana Tavares-Ferreira Anna Cervantes Geoffrey Funk Peter Horton Erin Vines Gregory Dussor Theodore J. Price |
| author_sort | Stephanie I. Shiers |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ac3c3c5ff0a84f6fa72812ed1f80f32b |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-ac3c3c5ff0a84f6fa72812ed1f80f32b2025-08-20T02:15:15ZengNature PortfolioNature Communications2041-17232025-05-0116111610.1038/s41467-025-59538-zNageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathyStephanie I. Shiers0Khadijah Mazhar1Andi Wangzhou2Rainer Haberberger3Joseph B. Lesnak4Nwasinachi A. Ezeji5Ishwarya Sankaranarayanan6Diana Tavares-Ferreira7Anna Cervantes8Geoffrey Funk9Peter Horton10Erin Vines11Gregory Dussor12Theodore J. Price13Department of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasAnatomy and Pathology, The University of AdelaideDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasSouthwest Transplant AllianceSouthwest Transplant AllianceSouthwest Transplant AllianceSouthwest Transplant AllianceDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasDepartment of Neuroscience, Center for Advanced Pain Studies, The University of Texas at DallasAbstract 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.https://doi.org/10.1038/s41467-025-59538-z |
| spellingShingle | Stephanie I. Shiers Khadijah Mazhar Andi Wangzhou Rainer Haberberger Joseph B. Lesnak Nwasinachi A. Ezeji Ishwarya Sankaranarayanan Diana Tavares-Ferreira Anna Cervantes Geoffrey Funk Peter Horton Erin Vines Gregory Dussor Theodore J. Price Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy Nature Communications |
| title | Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| title_full | Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| title_fullStr | Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| title_full_unstemmed | Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| title_short | Nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| title_sort | nageotte nodules in human dorsal root ganglia reveal neurodegeneration in diabetic peripheral neuropathy |
| url | https://doi.org/10.1038/s41467-025-59538-z |
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