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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00481621" target="_blank" >RIV/68378041:_____/17:00481621 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/17:10392688

Výsledek na webu

<a href="http://dx.doi.org/10.1038/s41467-017-01283-z" target="_blank" >http://dx.doi.org/10.1038/s41467-017-01283-z</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-017-01283-z" target="_blank" >10.1038/s41467-017-01283-z</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

<a href="/cs/project/GA17-21146S" target="_blank" >GA17-21146S: Hodnocení iontových kanálů a receptorů v lidských neurálních progenitorech derivovaných z IPS buněk behěm diferenciace na motoneurony.</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature Communications

ISSN

2041-1723

e-ISSN

—

Svazek periodika

8

Číslo periodika v rámci svazku

oct.

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

17

Strana od-do

—

Kód UT WoS článku

000413833000008

EID výsledku v databázi Scopus

2-s2.0-85032486894