Synaptic disruption and CREB‐regulated transcription are restored by K+ channel blockers in ALS
peer-reviewed
Erstveröffentlichung
2021-06-14Authors
Catanese, Alberto
Rajkumar, Sandeep
Sommer, Daniel
Freisem, Dennis
Wirth, Alexander
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.202013131Faculties
Fakultät für NaturwissenschaftenInstitutions
Institut für Anatomie und ZellbiologieUKU. Klinik für Innere Medizin I
UKU. Klinik für Neurologie
External cooperations
Deutsches Zentrum für Neurodegenerative ErkrankungenUniversité 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
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=GSE168831http://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
Metadata
Show full item recordDOI & 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
Citation formatter >