A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models
| Autor: | Tyzack, Giulia E., Hall, Claire E., Sibley, Christopher R., Cymes, Tomasz, Forostyak, Serhiy, Carlino, Giulia, Meyer, Ione F., Schiavo, Giampietro, Zhang, Su-Chun, Gibbons, George M., Newcombe, Jia, Patani, Rickie, Lakatos, András |
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| Přispěvatelé: | EDMOND J. SAFRA FOUNDATION, Lakatos, Andras [0000-0002-1301-2292], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
amyotrophic lateral sclerosis INTERLEUKIN-6 receptor Anti-Inflammatory Agents neurons sciatic nerve AMYOTROPHIC-LATERAL-SCLEROSIS ACTIVATION Mice SPINAL-CORD-INJURY SCAR FORMATION lcsh:Science humans health care economics and organizations Cells Cultured Motor Neurons Neurons Sciatic Nerve Neuroprotection animals Multidisciplinary Sciences ALZHEIMERS-DISEASE RECEPTORS Science & Technology - Other Topics iInterleukin-6 neuroprotection signal transduction Signal Transduction STAT3 Transcription Factor mice Receptor EphB1 Science axons anti-inflammatory agents Article SYNAPSE ELIMINATION male MD Multidisciplinary inbred C57BL motor neurons Animals Humans STAT3 transcription factor Inflammation disease models Science & Technology Amyotrophic Lateral Sclerosis astrocytes Axons Mice Inbred C57BL Disease Models Animal nervous system REACTIVE GLIOSIS inflammation Astrocytes cytology FACIAL MOTOR NUCLEUS cells lcsh:Q Transcriptome transcriptome |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-17 (2017) Nature Communications Tyzack, G E, Hall, C E, Sibley, C R, Cymes, T, Forostyak, S, Carlino, G, Meyer, I F, Schiavo, G, Zhang, S-C, Gibbons, G M, Newcombe, J, Patani, R & Lakatos, A 2017, ' A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models ', Nature Communications, vol. 8, no. 1, 1164 . https://doi.org/10.1038/s41467-017-01283-z |
| Popis: | 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. Astrocytes can have protective or detrimental effects on neurons during injury, but the molecular mechanisms that determine these different states are unresolved. Here the authors identify a pathway via neuronal EphB1 that induces neuroprotective signalling in astrocytes through ephrin-B1 mediated STAT3 activation, which is impaired in models of amyotrophic lateral sclerosis. |
| Databáze: | OpenAIRE |
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