Tyzack, GE;
Hall, CE;
Sibley, CR;
Cymes, T;
Forostyak, S;
Carlino, G;
Meyer, IF;
... Lakatos, A; + view all
(2017)
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Nature Communications
, 8
, Article 1164. 10.1038/s41467-017-01283-z.
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Abstract
Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanisms that determine these different responses are poorly understood. Here we show that ephrin type-B receptor 1 (EphB1) is upregulated in injured motor neurons, which in turn can activate astrocytes through ephrin-B1-mediated stimulation of signal transducer and activator of transcription-3 (STAT3). Transcriptional analysis shows that EphB1 induces a protective and anti-inflammatory signature in astrocytes, partially linked to the STAT3 network. This is distinct from the response evoked by interleukin (IL)-6 that is known to induce both pro inflammatory and anti-inflammatory processes. Finally, we demonstrate that the EphB1–ephrin-B1 pathway is disrupted in human stem cell derived astrocyte and mouse models of amyotrophic lateral sclerosis (ALS). Our work identifies an early neuronal help-me signal that activates a neuroprotective astrocytic response, which fails in ALS, and therefore represents an attractive therapeutic target.
| Type: | Article |
|---|---|
| Title: | A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-017-01283-z |
| Publisher version: | http://doi.org/10.1038/s41467-017-01283-z |
| Language: | English |
| Additional information: | © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, AMYOTROPHIC-LATERAL-SCLEROSIS, FACIAL MOTOR NUCLEUS, SPINAL-CORD-INJURY, REACTIVE GLIOSIS, SYNAPSE ELIMINATION, ALZHEIMERS-DISEASE, SCAR FORMATION, INTERLEUKIN-6, ACTIVATION, RECEPTORS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10037130 |
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