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

  1. Simon, Christian M.
  2. Rauskolb, Stefanie
  3. Gunnersen, Jennifer M.
  4. Holtmann, Bettina
  5. Drepper, Carsten
  6. Dombert, Benjamin
  7. Braga, Massimiliano
  8. Wiese, Stefan
  9. Jablonka, Sibylle
  10. Pühringer, Dirk
  11. Zielasek, Jürgen
  12. Hoeflich, Andreas ORCID logo
  13. Silani, Vincenzo
  14. Wolf, Eckhard
  15. Kneitz, Susanne
  16. Sommer, Claudia
  17. Toyka, Klaus V.
  18. Sendtner, Michael

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WeightNameValue
1000 Titel
  • Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy
1000 Autor/in
  1. Simon, Christian M. |
  2. Rauskolb, Stefanie |
  3. Gunnersen, Jennifer M. |
  4. Holtmann, Bettina |
  5. Drepper, Carsten |
  6. Dombert, Benjamin |
  7. Braga, Massimiliano |
  8. Wiese, Stefan |
  9. Jablonka, Sibylle |
  10. Pühringer, Dirk |
  11. Zielasek, Jürgen |
  12. Hoeflich, Andreas |
  13. Silani, Vincenzo |
  14. Wolf, Eckhard |
  15. Kneitz, Susanne |
  16. Sommer, Claudia |
  17. Toyka, Klaus V. |
  18. Sendtner, Michael |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Art der Datei
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-05-30
1000 Erschienen in
1000 Quellenangabe
  • 130(3): 373-387
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s00401-015-1446-8 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541707/ |
1000 Ergänzendes Material
  • https://link.springer.com/article/10.1007%2Fs00401-015-1446-8#SupplementaryMaterial |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • 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 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.
1000 Sacherschließung
lokal Diabetic polyneuropathy
lokal Motor nerve biopsy
lokal Neuropathy
lokal Neurotrophic factors
lokal Axonal degeneration
1000 Fachgruppe
  1. Biologie |
  2. Medizin |
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/creator/U2ltb24sIENocmlzdGlhbiBNLg==|https://frl.publisso.de/adhoc/creator/UmF1c2tvbGIsIFN0ZWZhbmll|https://frl.publisso.de/adhoc/creator/R3VubmVyc2VuLCBKZW5uaWZlciBNLg==|https://frl.publisso.de/adhoc/creator/SG9sdG1hbm4sIEJldHRpbmE=|https://frl.publisso.de/adhoc/creator/RHJlcHBlciwgQ2Fyc3Rlbg==|https://frl.publisso.de/adhoc/creator/RG9tYmVydCwgQmVuamFtaW4=|https://frl.publisso.de/adhoc/creator/QnJhZ2EsIE1hc3NpbWlsaWFubw==|https://frl.publisso.de/adhoc/creator/V2llc2UsIFN0ZWZhbg==|https://frl.publisso.de/adhoc/creator/SmFibG9ua2EsIFNpYnlsbGU=|https://frl.publisso.de/adhoc/creator/UMO8aHJpbmdlciwgRGlyaw==|https://frl.publisso.de/adhoc/creator/WmllbGFzZWssIErDvHJnZW4=|http://orcid.org/0000-0003-2018-2836|https://frl.publisso.de/adhoc/creator/U2lsYW5pLCBWaW5jZW56bw==|https://frl.publisso.de/adhoc/creator/V29sZiwgRWNraGFyZA==|https://frl.publisso.de/adhoc/creator/S25laXR6LCBTdXNhbm5l|https://frl.publisso.de/adhoc/creator/U29tbWVyLCBDbGF1ZGlh|https://frl.publisso.de/adhoc/creator/VG95a2EsIEtsYXVzIFYu|https://frl.publisso.de/adhoc/creator/U2VuZHRuZXIsIE1pY2hhZWw=
1000 Förderer
  1. German Research Foundation (DFG)
  2. Graduate School of Life Sciences, University of Wuerzburg
  3. European Community
  4. German Federal Ministry of Education and Research (BMBF)
  5. Sobek Foundation
  6. Hermann und Lilly Schilling–Stiftung im Stifterverband der Deutschen Industrie
1000 Fördernummer
  1. SFB 581; TP B4
  2. -
  3. 259867
  4. -
  5. -
  6. -
1000 Förderprogramm
  1. -
  2. -
  3. Health Seventh Framework Programme; EuroMOTOR
  4. -
  5. -
  6. -
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6410688.rdf
1000 Erstellt am 2018-10-22T10:23:07.818+0200
1000 Erstellt von 122
1000 beschreibt frl:6410688
1000 Bearbeitet von 218
1000 Zuletzt bearbeitet Tue Dec 18 12:46:02 CET 2018
1000 Objekt bearb. Tue Dec 18 12:46:01 CET 2018
1000 Vgl. frl:6410688
1000 Oai Id
  1. oai:frl.publisso.de:frl:6410688 |
1000 Sichtbarkeit Metadaten public
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