APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons
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...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
June 25, 2021
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| In: |
Proceedings of the National Academy of Sciences of the United States of America
Year: 2021, Jahrgang: 118, Heft: 26, Pages: 1-12 |
| ISSN: | 1091-6490 |
| DOI: | 10.1073/pnas.2011506118 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1073/pnas.2011506118 Verlag, lizenzpflichtig, Volltext: https://www.pnas.org/content/118/26/e2011506118 
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| Verfasserangaben: | Susann Ludewig, Ulrike Herrmann, Kristin Michaelsen-Preusse, Kristin Metzdorf, Jennifer Just, Charlotte Bold, Ulrike C. Müller, and Martin Korte |
MARC
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| 245 | 1 | 0 | |a APPsα rescues impaired Ca2+ homeostasis in APP- and APLP2-deficient hippocampal neurons |c Susann Ludewig, Ulrike Herrmann, Kristin Michaelsen-Preusse, Kristin Metzdorf, Jennifer Just, Charlotte Bold, Ulrike C. Müller, and Martin Korte |
| 246 | 3 | 3 | |a APPsα rescues impaired Ca 2+ homeostasis in APP- and APLP2-deficient hippocampal neurons |
| 246 | 3 | 3 | |a APPs alpha rescues impaired Ca two plus homeostasis in APP- and APLP two-deficient hippocampal neurons |
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| 520 | |a 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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| 700 | 1 | |a Michaelsen-Preusse, Kristin |e VerfasserIn |0 (DE-588)138809909 |0 (DE-627)606145540 |0 (DE-576)309201667 |4 aut | |
| 700 | 1 | |a Metzdorf, Kristin |e VerfasserIn |0 (DE-588)1256705187 |0 (DE-627)1800731892 |4 aut | |
| 700 | 1 | |a Just, Jennifer |e VerfasserIn |4 aut | |
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