| |  Online-Ressource |
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| Verfasst von: | Ludewig, Susann [VerfasserIn]  |
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| | Herrmann, Ulrike [VerfasserIn] |
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| | Michaelsen-Preusse, Kristin [VerfasserIn] |
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| | Metzdorf, Kristin [VerfasserIn] |
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| | Just, Jennifer [VerfasserIn] |
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| | Bold, Charlotte [VerfasserIn] |
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| | Müller, Ulrike C. [VerfasserIn] |
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| | Korte, Martin [VerfasserIn] |
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| Titel: | APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons |
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| Verf.angabe: | Susann Ludewig, Ulrike Herrmann, Kristin Michaelsen-Preusse, Kristin Metzdorf, Jennifer Just, Charlotte Bold, Ulrike C. Müller, and Martin Korte |
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| E-Jahr: | 2021 |
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| Jahr: | June 25, 2021 |
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| Umfang: | 12 S. |
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| Fussnoten: | Im Text ist "2+" hochgestellt ; Gesehen am 19.08.2021 |
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| Titel Quelle: | Enthalten in: National Academy of Sciences (Washington, DC)Proceedings of the National Academy of Sciences of the United States of America |
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| Ort Quelle: | Washington, DC : National Acad. of Sciences, 1915 |
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| Jahr Quelle: | 2021 |
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| Band/Heft Quelle: | 118(2021), 26, Artikel-ID e2011506118, Seite 1-12 |
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| ISSN Quelle: | 1091-6490 |
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| Abstract: | Alterations in Ca2+ homeostasis have been reported in several in vitro and in vivo studies using mice expressing the Alzheimer’s disease-associated transgenes, presenilin and the amyloid precursor protein (APP). While intense research focused on amyloid-β-mediated functions on neuronal Ca2+ handling, the physiological role of APP and its close homolog APLP2 is still not fully clarified. We now elucidate a mechanism to show how APP and its homolog APLP2 control neuronal Ca2+ handling and identify especially the ectodomain APPsα as an essential regulator of Ca2+ homeostasis. Importantly, we demonstrate that the loss of APP and APLP2, but not APLP2 alone, impairs Ca2+ handling, the refill of the endoplasmic reticulum Ca2+ stores, and synaptic plasticity due to altered function and expression of the SERCA-ATPase and expression of store-operated Ca2+ channel-associated proteins Stim1 and Stim2. Long-term AAV-mediated expression of APPsα, but not acute application of the recombinant protein, restored physiological Ca2+ homeostasis and synaptic plasticity in APP/APLP2 cDKO cultures. Overall, our analysis reveals an essential role of the APP family and especially of the ectodomain APPsα in Ca2+ homeostasis, thereby highlighting its therapeutic potential. |
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| DOI: | doi:10.1073/pnas.2011506118 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.1073/pnas.2011506118 |
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| | Volltext: https://www.pnas.org/content/118/26/e2011506118 |
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| | DOI: https://doi.org/10.1073/pnas.2011506118 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Alzheimer’s disease |
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| | APP |
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| | Ca2+ homeostasis |
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| | synaptic plasticity |
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| K10plus-PPN: | 1767332793 |
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| Verknüpfungen: | → Zeitschrift |
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APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons / Ludewig, Susann [VerfasserIn]; June 25, 2021 (Online-Ressource)
