β-Secretase Cleavage of the Fly Amyloid Precursor Protein Is Required for Glial Survival

Bolkan, Bonnie J.; Triphan, Tilman; Kretzschmar, Doris

β-Secretase Cleavage of the Fly Amyloid Precursor Protein Is Required for Glial Survival

Dateien

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Datum

2012

Autor:innen

Bolkan, Bonnie J.

Triphan, Tilman

Kretzschmar, Doris

DOI (zitierfähiger Link)

https://doi.org/10.1523/JNEUROSCI.0228-12.2012

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Journal of Neuroscience. Society for Neuroscience. 2012, 32(46), pp. 16181-16192. ISSN 0270-6474. eISSN 1529-2401. Available under: doi: 10.1523/JNEUROSCI.0228-12.2012

Zusammenfassung

β-secretase (or BACE1) is the key enzyme in the production of β-amyloid (Aβ), which accumulates in the senile plaques characteristic for Alzheimer's disease. Consequently, the lack of BACE1 prevents β-processing of the amyloid precursor protein and Aβ production, which made it a promising target for drug development. However, the loss of BACE1 is also detrimental, leading to myelination defects and altered neuronal activity, functions that have been associated with the cleavage of Neuregulin and a voltage-gated sodium channel subunit. Here we show that the Drosophila ortholog of BACE, dBACE, is required for glial survival. Cell-specific knockdown experiments reveal that this is a non-cell autonomous function, as a knockdown of dBACE in photoreceptor neurons leads to progressive degeneration of glia in their target zone, the lamina. Interestingly, this phenotype is suppressed by the loss of the fly amyloid precursor protein (APPL), whereas a secretion-deficient form of APPL enhances the degeneration. This shows that full-length APPL in neurons promotes the death of neighboring glial cells and that β-processing of APPL is needed to prevent glial death. These results therefore not only demonstrate a novel function for an APP protein in glia, but they also show this function specifically requires regulation by β-cleavage.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Zitieren

ISO 690

BOLKAN, Bonnie J., Tilman TRIPHAN, Doris KRETZSCHMAR, 2012. β-Secretase Cleavage of the Fly Amyloid Precursor Protein Is Required for Glial Survival. In: Journal of Neuroscience. Society for Neuroscience. 2012, 32(46), pp. 16181-16192. ISSN 0270-6474. eISSN 1529-2401. Available under: doi: 10.1523/JNEUROSCI.0228-12.2012

BibTex

@article{Bolkan2012-11-14Secre-52838,
  year={2012},
  doi={10.1523/JNEUROSCI.0228-12.2012},
  title={β-Secretase Cleavage of the Fly Amyloid Precursor Protein Is Required for Glial Survival},
  number={46},
  volume={32},
  issn={0270-6474},
  journal={Journal of Neuroscience},
  pages={16181--16192},
  author={Bolkan, Bonnie J. and Triphan, Tilman and Kretzschmar, Doris}
}

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