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

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

doi:10.1038/s41467-019-09886-4

アイテム詳細

登録内容を編集ファイル形式で保存

一時保存へ追加

タグ情報を表示リリース履歴を表示詳細要約

公開

学術論文

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

MPS-Authors

/persons/resource/persons182152

Fledrich, Robert
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232140

Akkermann, Dagmar
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224786

Schütza, Vlad
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182057

Abdelaal, Tamer A. M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons224792

Hermes, Doris
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons232141

Schäffner, Erik
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons207307

Soto Bernardini, Maria Clara
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182462

Götze, Tilmann
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182248

Klink, Axel
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182268

Kusch, Kathrin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182265

Kungl, Theresa
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182306

Möbius, Wiebke
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182406

Sereda, Michael Werner
Molecular and translational neurology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182402

Schwab, Markus H.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182320

Nave, Klaus-Armin
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182427

Stassart, Ruth M.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

External Resource

There are no locators available

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

フルテキスト (公開)

Fledrich_19.pdf
(出版社版), 6MB

付随資料 (公開)

There is no public supplementary material available

引用

Fledrich, R., Akkermann, D., Schütza, V., Abdelaal, T. A. M., Hermes, D., Schäffner, E., Soto Bernardini, M. C., Götze, T., Klink, A., Kusch, K., Krueger, M., Kungl, T., Frydrychowicz, C., Möbius, W., Brück, W., Mueller, W. C., Bechmann, I., Sereda, M. W., Schwab, M. H., Nave, K.-A., & Stassart, R. M. (2019). NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies. Nature Communications, 10:. doi:10.1038/s41467-019-09886-4.

引用: https://hdl.handle.net/21.11116/0000-0003-5571-E

要旨

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.