NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies

2019 | journal article. A publication with affiliation to the University of Göttingen.

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​NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies​
Fledrich, R.; Akkermann, D.; Schütza, V.; Abdelaal, T. A.; Hermes, D.; Schäffner, E. & Soto-Bernardini, M. C. et al.​ (2019) 
Nature Communications10(1) art. 1467​.​ DOI: 

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Fledrich, Robert; Akkermann, Dagmar; Schütza, Vlad; Abdelaal, Tamer A.; Hermes, Doris; Schäffner, Erik; Soto-Bernardini, M. Clara; Götze, Tilmann; Klink, Axel; Kusch, Kathrin; Krueger, Martin; Kungl, Theresa; Frydrychowicz, Clara; Möbius, Wiebke ; Brück, Wolfgang; Mueller, Wolf C.; Bechmann, Ingo; Sereda, Michael W.; Schwab, Markus H.; Nave, Klaus-Armin; Stassart, Ruth M.
In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases. Genetic disruption of Schwann cell-derived NRG1 signalling in a mouse model of Charcot-Marie-Tooth Disease 1A (CMT1A), suppresses hypermyelination and the formation of onion bulbs. Transgenic overexpression of NRG1-I in Schwann cells on a wildtype background is sufficient to mediate an interaction between Schwann cells via an ErbB2 receptor-MEK/ERK signaling axis, which causes onion bulb formations and results in a peripheral neuropathy reminiscent of CMT1A. We suggest that diseased Schwann cells mount a regeneration program that is beneficial in acute nerve injury, but that overstimulation of Schwann cells in chronic neuropathies is detrimental.
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