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Synaptic disruption and CREB‐regulated transcription are restored by K+ channel blockers in ALS

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peer-reviewed

Erstveröffentlichung
2021-06-14
Authors
Catanese, Alberto
Rajkumar, Sandeep
Sommer, Daniel
Freisem, Dennis
Wirth, Alexander
et al.
Wissenschaftlicher Artikel


Published in
EMBO Molecular Medicine ; 13 (2021), 7. - Art.-Nr. e13131. - ISSN 1757-4684. - eISSN 1757-4676
Link to original publication
https://dx.doi.org/10.15252/emmm.202013131
Faculties
Fakultät für Naturwissenschaften
Institutions
Institut für Anatomie und Zellbiologie
UKU. Klinik für Innere Medizin I
UKU. Klinik für Neurologie
External cooperations
Deutsches Zentrum für Neurodegenerative Erkrankungen
Université de Paris
Imagine Institute des maladies génétiques
Document version
published version (publisher's PDF)
Abstract
Synopsis image The lack of an effective treatment for ALS is calling for the development of novel therapeutic strategies. By using hiPSC‐derived motoneurons and focusing on synapse‐related processes, we provide new molecular targets rescuing the degenerative processes and neuronal loss in ALS. Human C9orf72‐mutant motoneurons are characterized by reduced expression of synaptic gene, progressive loss of CREB activity and synapse loss. Similar alterations are observed also in motoneurons harboring TBK1 pathogenic mutations, and in primary neurons upon overexpression of poly(GA) aggregates. The K+ channel blockers Apamin and XE991 revert the CREB‐dependent loss of synaptic contacts and rescue the degenerative phenotypes of ALS motoneurons.
DFG Project THU
SFB 1149 / Gefahrenantwort, Störfaktoren und regeneratives Potential nach akutem Trauma / DFG / 251293561
GRK 1789 / CEMMA / Zelluläre und molekulare Mechanismen der Alterung / DFG / 194266605
Is supplemented by
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE168831
http://www.ebi.ac.uk/pride/archive/projects/PXD020316
https://www.embopress.org/action/downloadSupplement?doi=10.15252%2Femmm.202013131&file=emmm202013131-sup-0001-Appendix.pdf
https://www.embopress.org/action/downloadSupplement?doi=10.15252%2Femmm.202013131&file=emmm202013131-sup-0002-EVFigs.pdf
https://www.embopress.org/action/downloadSupplement?doi=10.15252%2Femmm.202013131&file=emmm202013131-sup-0003-SDataEV.zip
Subject headings
[GND]: Myatrophische Lateralsklerose | Motoneuron | Synapse
[MeSH]: Amyotrophic lateral sclerosis; Therapy | Motor neurons | Synapses
[Free subject headings]: ALS | CREB | hiPSC
[DDC subject group]: DDC 610 / Medicine & health
License
CC BY 4.0 International
https://creativecommons.org/licenses/by/4.0/

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-40024

Catanese, Alberto et al. (2021): Synaptic disruption and CREB‐regulated transcription are restored by K+ channel blockers in ALS. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-40024
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