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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Robert Fledrich, Dagmar Akkermann, Vlad Schütza, Tamer A. Abdelaal, Doris Hermes, Erik Schäffner, M. Clara Soto-Bernardini, Tilmann Götze, Axel Klink, Kathrin Kusch, Martin Krueger, Theresa Kungl, Clara Frydrychowicz, Wiebke Möbius, Wolfgang Brück, Wolf C. Mueller, Ingo Bechmann, Michael W. Sereda, Markus H. Schwab, Klaus-Armin Nave, Ruth M. Stassart

ABSTRACT

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. More... »

PAGES

1467

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-019-09385-6

DOI

http://dx.doi.org/10.1038/s41467-019-09385-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113158173

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30931926


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