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A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models
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SYSNO ASEP 0481621 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models Tvůrce(i) Tyzack, G.E. (GB)
Hall, E.C. (GB)
Sibley, Ch.R. (GB)
Cymes, T. (GB)
Forostyak, Serhiy (UEM-P) RID, ORCID
Carlino, G. (GB)
Meyer, I.F. (CZ)
Schiavo, G. (GB)
Zhang, S.Ch. (GB)
Gibbons, G.M. (GB)
Newcombe, J. (GB)
Patani, R. (GB)
Lakatos, A. (GB)Zdroj.dok. Nature Communications. - : Nature Publishing Group
Roč. 8, oct. (2017), s. 1164Poč.str. 17 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova amyotrophic-lateral-sclerosis ; facial motor nucleus ; spinal-cord-injury Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Neurosciences (including psychophysiology CEP GA17-21146S GA ČR - Grantová agentura ČR Institucionální podpora UEM-P - RVO:68378041 UT WOS 000413833000008 EID SCOPUS 85032486894 DOI 10.1038/s41467-017-01283-z Anotace 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. Pracoviště Ústav experimentální medicíny Kontakt Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Rok sběru 2018
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