Exploring Structural and Molecular Features of Sciatic Nerve Lesions in Diabetic Neuropathy: Unveiling Pathogenic Pathways and Targets
Lesioned fascicles (LFs) in the sciatic nerves of individuals with diabetic neuropathy (DN) correlate with clinical symptom severity. This study aimed to characterize the structural and molecular composition of these lesions to better understand DN pathogenesis. Sciatic nerves from amputees with and without type 2 diabetes (T2D) were examined using ex vivo magnetic resonance neurography, in vitro imaging, and proteomic analysis. Lesions were only found in T2D donors and exhibited significant structural abnormalities, including axonal degeneration, demyelination, and impaired blood-nerve barrier (BNB). Although non-LFs from T2D donors showed activation of neuroprotective pathways, LFs lacked this response and instead displayed increased complement activation via the classical pathway. The detection of liver-derived acute-phase proteins suggests that BNB disruption facilitates harmful interorgan communication between the liver and nerves. These findings reveal key molecular mechanisms contributing to DN and highlight potential targets for therapeutic intervention. Article Highlights
Authors
- Ζoltan Κender (ORCID: https://orcid.org/0000-0003-0745-1587)
- Maxime Le Marois
- Dittmar Böckler (ORCID: https://orcid.org/0000-0003-2421-2019)
- Julia Szendroedi (ORCID: https://orcid.org/0000-0002-5185-8168)
- Martin Bendszus (ORCID: https://orcid.org/0000-0002-9094-6769)
- Joachim Weis (ORCID: https://orcid.org/0000-0003-3280-6773)
- Dominic Helm (ORCID: https://orcid.org/0000-0001-9321-2069)
- Susanne Dihlmann (ORCID: https://orcid.org/0000-0002-3737-7755)
- Andreas S. Peters (ORCID: https://orcid.org/0000-0002-1347-7575)
- Martin Schneider (ORCID: https://orcid.org/0000-0001-8215-7359)
- Ingrid Haußer (ORCID: https://orcid.org/0000-0002-1095-4962)
- Åsa Hidmark
- Rémi Longuespée (ORCID: https://orcid.org/0000-0003-2003-1886)
- Constantin Schwab (ORCID: https://orcid.org/0000-0002-0979-2943)
- Dániel Schwarz (ORCID: https://orcid.org/0000-0002-9017-8245)
- Peter P. Nawroth (ORCID: https://orcid.org/0000-0002-6134-7804)
- Stephan Herzig (ORCID: https://orcid.org/0000-0003-3950-3652)
- Sabine Heiland (ORCID: https://orcid.org/0000-0002-2796-3451)
- Thomas Henry Fleming (ORCID: https://orcid.org/0000-0002-3232-4515)
- Manuel Fischer (ORCID: https://orcid.org/0000-0001-7459-1024)
- Volker Sturm (ORCID: https://orcid.org/0000-0001-8681-9372)
- Bastian Eichmüller
Institutions
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Helmholtz Zentrum München (DE)
- Universitätsklinikum Aachen (DE)
- Diabetesinstitut Heidelberg (DE)
- Westfälische Hochschule (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- German Center for Diabetes Research (DE)
- Heinrich Heine University Düsseldorf (DE)
- Technical University of Munich (DE)
- RWTH Aachen University (DE)
Publication Details
- Journal
- Diabetes
- Published
- 2024-10-17
- DOI
- https://doi.org/10.2337/db24-0493
- Citations
- 3
- Primary Topic
- Pain Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.98