Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease

  1. Grochowska, Katarzyna ORCID logo
  2. GM, Gomes ORCID logo
  3. Raman,Rajeev
  4. Kaushik, Rahul
  5. Sosulina, Liudmila
  6. Kaneko, Hiroshi
  7. Oelschlegel, Anja M.
  8. YUANXIANG, PingAn ORCID logo
  9. Reyes-Resina, Irene ORCID logo
  10. Bayraktar, Gonca
  11. Samer, Sebastian
  12. Spilker, Christina ORCID logo
  13. Woo, Marcel Seungsu ORCID logo
  14. Morawski, Markus ORCID logo
  15. Goldschmidt, Jürgen ORCID logo
  16. Friese, Manuel A. ORCID logo
  17. Rossner, Steffen
  18. Navarro, Gemma
  19. Remy, Stefan ORCID logo
  20. Reissner, Carsten ORCID logo
  21. Karpova, Anna ORCID logo
  22. Kreutz, Michael R. ORCID logo

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The EMBO Journal - 2023 - Grochowska - Jacob‐induced transcriptional inactivation of CREB promotes A ‐induced synapse loss.pdf 15,12MB
WeightNameValue
1000 Titel
  • Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease
1000 Autor/in
  1. Grochowska, Katarzyna |
  2. GM, Gomes |
  3. Raman,Rajeev |
  4. Kaushik, Rahul |
  5. Sosulina, Liudmila |
  6. Kaneko, Hiroshi |
  7. Oelschlegel, Anja M. |
  8. YUANXIANG, PingAn |
  9. Reyes-Resina, Irene |
  10. Bayraktar, Gonca |
  11. Samer, Sebastian |
  12. Spilker, Christina |
  13. Woo, Marcel Seungsu |
  14. Morawski, Markus |
  15. Goldschmidt, Jürgen |
  16. Friese, Manuel A. |
  17. Rossner, Steffen |
  18. Navarro, Gemma |
  19. Remy, Stefan |
  20. Reissner, Carsten |
  21. Karpova, Anna |
  22. Kreutz, Michael R. |
1000 Erscheinungsjahr
  • 2023
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2023-01-03
1000 Erschienen in
1000 Quellenangabe
  • 42(4):e112453
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2023
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.15252/embj.2022112453 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9929644/ |
1000 Ergänzendes Material
  • https://www.embopress.org/doi/full/10.15252/embj.2022112453#support-information-section |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Synaptic dysfunction caused by soluble β-amyloid peptide (Aβ) is a hallmark of early-stage Alzheimer's disease (AD), and is tightly linked to cognitive decline. By yet unknown mechanisms, Aβ suppresses the transcriptional activity of cAMP-responsive element-binding protein (CREB), a master regulator of cell survival and plasticity-related gene expression. Here, we report that Aβ elicits nucleocytoplasmic trafficking of Jacob, a protein that connects a NMDA-receptor-derived signalosome to CREB, in AD patient brains and mouse hippocampal neurons. Aβ-regulated trafficking of Jacob induces transcriptional inactivation of CREB leading to impairment and loss of synapses in mouse models of AD. The small chemical compound Nitarsone selectively hinders the assembly of a Jacob/LIM-only 4 (LMO4)/ Protein phosphatase 1 (PP1) signalosome and thereby restores CREB transcriptional activity. Nitarsone prevents impairment of synaptic plasticity as well as cognitive decline in mouse models of AD. Collectively, the data suggest targeting Jacob protein-induced CREB shutoff as a therapeutic avenue against early synaptic dysfunction in AD.
1000 Sacherschließung
lokal Jacob
lokal Amyloid pathology
lokal early synaptic dysfunction
lokal Alzheimer's disease
lokal CREB
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0001-8298-176X|https://orcid.org/0000-0001-8566-4284|https://frl.publisso.de/adhoc/uri/UmFtYW4sUmFqZWV2|https://frl.publisso.de/adhoc/uri/S2F1c2hpaywgUmFodWw=|https://frl.publisso.de/adhoc/uri/U29zdWxpbmEsIExpdWRtaWxh|https://frl.publisso.de/adhoc/uri/S2FuZWtvLCBIaXJvc2hp|https://frl.publisso.de/adhoc/uri/T2Vsc2NobGVnZWwsIEFuamEgTS4=|https://orcid.org/0000-0002-3746-3282|https://orcid.org/0000-0003-2077-2537|https://frl.publisso.de/adhoc/uri/QmF5cmFrdGFyLCBHb25jYQ==|https://frl.publisso.de/adhoc/uri/U2FtZXIsIFNlYmFzdGlhbg==|https://orcid.org/0000-0002-7996-7673|https://orcid.org/0000-0002-1306-2708|https://orcid.org/0000-0002-3817-5186|https://orcid.org/0000-0002-6986-9914|https://orcid.org/0000-0001-6380-2420|https://frl.publisso.de/adhoc/uri/Um9zc25lciwgU3RlZmZlbg==|https://frl.publisso.de/adhoc/uri/TmF2YXJybywgR2VtbWE=|https://orcid.org/0000-0002-3386-1662|https://orcid.org/0000-0002-5496-9971|https://orcid.org/0000-0001-7423-4764|https://orcid.org/0000-0003-0575-6950
1000 Label
1000 Förderer
  1. Deutsche Forschungsgemeinschaft |
  2. Bundesministerium für Bildung und Forschung |
  3. EU Joint Programme – Neurodegenerative Disease Research |
  4. Leibniz-Gemeinschaft |
  5. Seventh Framework Programme |
  6. Alzheimer's Association |
  7. Deutscher Akademischer Austauschdienst |
  8. Alexander von Humboldt-Stiftung |
  9. Federal State of Saxony-Anhalt |
  10. European Regional Development Fund |
  11. Projekt DEAL |
1000 Fördernummer
  1. RI_00489; Kr 1879/9-1/FOR 2419, FOR 5228 RP6; Kr1879/10-1; CRC 1436 TPA02, TPA04, Z01; GRK1167; TPA3; CRC 779 TPB8; FOR 5228 RP6
  2. 01GQ1421B
  3. 01ED1613
  4. SAW 2017, 2018, 2019 Neurotranslation, SyMetAge, SynERCA
  5. 289581
  6. AARFD-17-503612
  7. -
  8. 99999.001756/2014-01
  9. -
  10. ZS/2016/04/78113; ZS/2016/04/78120
  11. -
1000 Förderprogramm
  1. Research Training Group 2413 Synage
  2. Energi
  3. STAD
  4. -
  5. H2020 Priority Excellent Science, Marie Sklodowska-Curie Actions (MSCA) MC-ITN NPlast
  6. -
  7. CAPES scholarship
  8. -
  9. -
  10. Center for Behavioral Brain Sciences (CBBS) Neuronetworl
  11. Open Access Funding
1000 Dateien
  1. Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease
    Jacob-induced transcriptional inactivation of CREB promotes Aβ-induced synapse loss in Alzheimer's disease
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm Research Training Group 2413 Synage
    1000 Fördernummer RI_00489; Kr 1879/9-1/FOR 2419, FOR 5228 RP6; Kr1879/10-1; CRC 1436 TPA02, TPA04, Z01; GRK1167; TPA3; CRC 779 TPB8; FOR 5228 RP6
  2. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm Energi
    1000 Fördernummer 01GQ1421B
  3. 1000 joinedFunding-child
    1000 Förderer EU Joint Programme – Neurodegenerative Disease Research |
    1000 Förderprogramm STAD
    1000 Fördernummer 01ED1613
  4. 1000 joinedFunding-child
    1000 Förderer Leibniz-Gemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer SAW 2017, 2018, 2019 Neurotranslation, SyMetAge, SynERCA
  5. 1000 joinedFunding-child
    1000 Förderer Seventh Framework Programme |
    1000 Förderprogramm H2020 Priority Excellent Science, Marie Sklodowska-Curie Actions (MSCA) MC-ITN NPlast
    1000 Fördernummer 289581
  6. 1000 joinedFunding-child
    1000 Förderer Alzheimer's Association |
    1000 Förderprogramm -
    1000 Fördernummer AARFD-17-503612
  7. 1000 joinedFunding-child
    1000 Förderer Deutscher Akademischer Austauschdienst |
    1000 Förderprogramm CAPES scholarship
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer Alexander von Humboldt-Stiftung |
    1000 Förderprogramm -
    1000 Fördernummer 99999.001756/2014-01
  9. 1000 joinedFunding-child
    1000 Förderer Federal State of Saxony-Anhalt |
    1000 Förderprogramm -
    1000 Fördernummer -
  10. 1000 joinedFunding-child
    1000 Förderer European Regional Development Fund |
    1000 Förderprogramm Center for Behavioral Brain Sciences (CBBS) Neuronetworl
    1000 Fördernummer ZS/2016/04/78113; ZS/2016/04/78120
  11. 1000 joinedFunding-child
    1000 Förderer Projekt DEAL |
    1000 Förderprogramm Open Access Funding
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6440789.rdf
1000 Erstellt am 2023-03-20T11:15:11.823+0100
1000 Erstellt von 242
1000 beschreibt frl:6440789
1000 Bearbeitet von 25
1000 Zuletzt bearbeitet Wed Mar 22 14:14:46 CET 2023
1000 Objekt bearb. Wed Mar 22 14:14:26 CET 2023
1000 Vgl. frl:6440789
1000 Oai Id
  1. oai:frl.publisso.de:frl:6440789 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

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