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Open Access 01-09-2015 | Original Paper

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

Authors: 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

Published in: Acta Neuropathologica | Issue 3/2015

Abstract

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.

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Title: Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy
Authors: 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
Publication date: 01-09-2015
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2015
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-015-1446-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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