A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models

Title: A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models
Author(s): Tyzack, GE
Hall, CE
Sibley, CR
Cymes, T
Forostyak, S
Carlino, G
Meyer, IF
Schiavo, G
Zhang, S-C
Gibbons, GM
Newcombe, J
Patani, R
Lakatos, A
Item Type: Journal Article
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.
Publication Date: 27-Oct-2017
Date of Acceptance: 6-Sep-2017
URI: http://hdl.handle.net/10044/1/54622
DOI: https://dx.doi.org/10.1038/s41467-017-01283-z
ISSN: 2041-1723
Publisher: NATURE PUBLISHING GROUP
Journal / Book Title: NATURE COMMUNICATIONS
Volume: 8
Copyright Statement: © 2017 The Author(s). Open Access. 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/.
Sponsor/Funder: EDMOND J. SAFRA FOUNDATION
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
MD Multidisciplinary
Publication Status: Published
Article Number: ARTN 1164
Appears in Collections:Department of Medicine
Faculty of Medicine



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