Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy
CM Simon, S Rauskolb, JM Gunnersen, B Holtmann, C Drepper, B Dombert, M Braga, S Wiese, S Jablonka, D Pühringer, J Zielasek, A Hoeflich, V Silani, E Wolf, S Kneitz, C Sommer, KV Toyka, M Sendtner
Acta Neuropathologica | Springer Nature | Published : 2015
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 red..View full abstract
Awarded by DFG
Awarded by European Community's Health Seventh Framework Programme
We thank Katrin Walter, Simone Rink, Manuela Kohles, Christian Mehling, Lydia Biko and Regine Sendtner for technical assistance and Robert Blum for help on the confocal microscope. This work was supported by the DFG, Grant SFB 581, TP B4, the Graduate School of Life Sciences, University of Wuerzburg, the European Community's Health Seventh Framework Programme under Grant agreement 259867 (EuroMOTOR), the German Government (BMBF) funded Motoneuron Disease Network, The Sobek Foundation, and the Hermann und Lilly Schilling-Stiftung im Stifterverband der Deutschen Industrie. The authors have no financial interests.