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Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy

Please always quote using this URN: urn:nbn:de:bvb:20-opus-154569
  • Diabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen inDiabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen in DNP. Motor axon degeneration was also observed in mice in which the IGF1 receptor(IGF1R) was conditionally depleted in motoneurons, indicating that reduced activity of IGF1 on IGF1R in motoneurons is responsible for the observed effect. These data provide evidence that elevated expression of IGFBP5 in diabetic nerves reduces the availability of IGF1 for IGF1R on motor axons, thus leading to progressive neurodegeneration. Inhibition of IGFBP5 could thus offer novel treatment strategies for DNP.show moreshow less

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Metadaten
Author: Christian M. Simon, Stefanie Rauskolb, Jennifer M. Gunnersen, Bettina Holtmann, Carsten Drepper, Benjamin Dombert, Massimiliano Braga, Stefan Wiese, Sibylle Jablonka, Dirk Pühringer, Jürgen Zielasek, Andreas Hoeflich, Vincenzo Silani, Eckhard Wolf, Susanne Kneitz, Claudia Sommer, Klaus V. Toyka, Michael Sendtner
URN:urn:nbn:de:bvb:20-opus-154569
Document Type:Journal article
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Medizinische Fakultät / Neurologische Klinik und Poliklinik
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Acta Neuropathologica
Year of Completion:2015
Volume:130
Source:Acta Neuropathologica (2015) 130:373–387. DOI: 10.1007/s00401-015-1446-8
DOI:https://doi.org/10.1007/s00401-015-1446-8
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:Axonal degeneration; Diabetic polyneuropathy; Motor nerve biopsy; Neuropathy; Neurotrophic factors
Release Date:2017/11/06
First Page:373
Last Page:387
EU-Project number / Contract (GA) number:259867
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International