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sAPPα antagonizes dendritic degeneration and neuron death triggered by proteasomal stress

Impaired proteasomal function is a major hallmark in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). Here we investigated the biological properties of the secreted cleavage product of APP (sAPPalpha) in antagonizing stress signalling, dendritic degeneratio...

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Main Authors: Copanaki, Ekaterini (Author) , Chang, Steffi (Author) , Vlachos, Andreas (Author) , Tschäpe, Jakob-Andreas (Author) , Müller, Ulrike C. (Author) , Kögel, Donat (Author) , Deller, Thomas (Author)
Format: Article (Journal)
Language:English
Published: 21 May 2010
In: Molecular and cellular neuroscience
Year: 2010, Volume: 44, Issue: 4, Pages: 386-393
ISSN:1095-9327
DOI:10.1016/j.mcn.2010.04.007
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.mcn.2010.04.007
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Author Notes:Ekaterini Copanaki, Steffi Chang, Andreas Vlachos, Jakob-A. Tschäpe, Ulrike C. Müller, Donat Kögel, Thomas Deller
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Summary:Impaired proteasomal function is a major hallmark in the pathophysiology of neurodegenerative diseases, including Alzheimer's disease (AD). Here we investigated the biological properties of the secreted cleavage product of APP (sAPPalpha) in antagonizing stress signalling, dendritic degeneration and neuronal cell death induced by the proteasome inhibitor epoxomicin. Analysis of executioner caspase activation demonstrated that sAPPalpha was able to protect PC12 cells from apoptosis triggered by epoxomicin, as well as by genotoxic stress (UV irradiation). This anti-apoptotic effect of sAPPalpha was associated with inhibition of the stress-triggered c-Jun N-terminal kinase (JNK)-signalling pathway. The anti-apoptotic effect of sAPPalpha could also be confirmed in organotypic slice cultures of Thy1-GFP mouse hippocampi. Confocal time-lapse imaging of CA1 pyramidal neurons revealed that preincubation with sAPPalpha preserves the structural integrity of neurons after epoxomicin treatment. Taken together, our data demonstrate that sAPPalpha is neuroprotective under conditions of proteasomal stress.
Item Description:Gesehen am 15.06.2023
Physical Description:Online Resource
ISSN:1095-9327
DOI:10.1016/j.mcn.2010.04.007

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