The interaction of beta-amyloid protein with cellular membranes stimulates its own production

Imke Peters; Urule Igbavboa; Tanja Schütt; Schamim Haidari; Ulrike Hartig; Ximena Rosello; Steffi Böttner; Ekaterini Copanaki; Thomas Deller; Donat Kögel; W. Gibson Wood; Walter E. Müller; Gunter P. Eckert

doi:10.1016/j.bbamem.2009.01.012

The interaction of beta-amyloid protein with cellular membranes stimulates its own production

Imke Peters, Urule Igbavboa, Tanja Schütt, Schamim Haidari, Ulrike Hartig, Ximena Rosello, Steffi Böttner, Ekaterini Copanaki, Thomas Deller, Donat Kögel, W. Gibson Wood, Walter E. Müller, Gunter P. Eckert

Pharmacology

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

Abstract

Gradual changes in steady-state levels of beta amyloid peptides (Aβ) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Aβ is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Cleavage of APP strongly depends on membrane properties. Since Aβ perturbs cell membrane fluidity, the cell membrane may be the location where the neurotoxic cascade of Aβ is initiated. Therefore, we tested effects of oligomeric Aβ on membrane fluidity of whole living cells, the impact of exogenous and cellular Aβ on the processing of APP and the role of GM-1 ganglioside. We present evidence that oligoAβ_(1-40) stimulates the amyloidogenic processing of APP by reducing membrane fluidity and complexing with GM-1 ganglioside. This dynamic action of Aβ may start a vicious circle, where endogenous Aβ stimulates its own production. Based on our novel findings, we propose that oligoAβ_(1-40) accelerates the proteolytic cleavage of APP by decreasing membrane fluidity.

Original language	English (US)
Pages (from-to)	964-972
Number of pages	9
Journal	Biochimica et Biophysica Acta - Biomembranes
Volume	1788
Issue number	5
DOIs	https://doi.org/10.1016/j.bbamem.2009.01.012
State	Published - May 2009

Bibliographical note

Funding Information:
This work was supported in part by grants from the Hanna Bragard-Apfel Foundation, Alzheimer Forschung Initiative e.V. (AFI #07821 to D.K. and G.P.E, #06808 to T.D. and #08823 to G.P.E.) and the National Institutes of Health AG-23524, AG-18357 and the Department of Veterans Affairs to W.G.W. We thank Dr. Tobias Hartmann, Homburg, Germany for providing us with SH-SY5YAβPP695 cells and Dr. Paul M. Mathews, Nathan Kline Institute, Orangeburg, NY, for providing us with the mouse IgG C1/6.1 antibody. We also acknowledge the technical help of Dr. Eltahmash Israr, Claudia Jourdan and Anke Biczysko.

Keywords

APP
Alzheimer
Beta amyloid
GM-1 ganglioside
Membrane fluidity

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10.1016/j.bbamem.2009.01.012

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Peters, I., Igbavboa, U., Schütt, T., Haidari, S., Hartig, U., Rosello, X., Böttner, S., Copanaki, E., Deller, T., Kögel, D., Wood, W. G., Müller, W. E., & Eckert, G. P. (2009). The interaction of beta-amyloid protein with cellular membranes stimulates its own production. Biochimica et Biophysica Acta - Biomembranes, 1788(5), 964-972. https://doi.org/10.1016/j.bbamem.2009.01.012

Peters, I, Igbavboa, U, Schütt, T, Haidari, S, Hartig, U, Rosello, X, Böttner, S, Copanaki, E, Deller, T, Kögel, D, Wood, WG, Müller, WE & Eckert, GP 2009, 'The interaction of beta-amyloid protein with cellular membranes stimulates its own production', Biochimica et Biophysica Acta - Biomembranes, vol. 1788, no. 5, pp. 964-972. https://doi.org/10.1016/j.bbamem.2009.01.012

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abstract = "Gradual changes in steady-state levels of beta amyloid peptides (Aβ) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Aβ is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Cleavage of APP strongly depends on membrane properties. Since Aβ perturbs cell membrane fluidity, the cell membrane may be the location where the neurotoxic cascade of Aβ is initiated. Therefore, we tested effects of oligomeric Aβ on membrane fluidity of whole living cells, the impact of exogenous and cellular Aβ on the processing of APP and the role of GM-1 ganglioside. We present evidence that oligoAβ(1-40) stimulates the amyloidogenic processing of APP by reducing membrane fluidity and complexing with GM-1 ganglioside. This dynamic action of Aβ may start a vicious circle, where endogenous Aβ stimulates its own production. Based on our novel findings, we propose that oligoAβ(1-40) accelerates the proteolytic cleavage of APP by decreasing membrane fluidity.",

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note = "Funding Information: This work was supported in part by grants from the Hanna Bragard-Apfel Foundation, Alzheimer Forschung Initiative e.V. (AFI #07821 to D.K. and G.P.E, #06808 to T.D. and #08823 to G.P.E.) and the National Institutes of Health AG-23524, AG-18357 and the Department of Veterans Affairs to W.G.W. We thank Dr. Tobias Hartmann, Homburg, Germany for providing us with SH-SY5YAβPP695 cells and Dr. Paul M. Mathews, Nathan Kline Institute, Orangeburg, NY, for providing us with the mouse IgG C1/6.1 antibody. We also acknowledge the technical help of Dr. Eltahmash Israr, Claudia Jourdan and Anke Biczysko. ",

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AU - Schütt, Tanja

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AU - Hartig, Ulrike

AU - Rosello, Ximena

AU - Böttner, Steffi

AU - Copanaki, Ekaterini

AU - Deller, Thomas

AU - Kögel, Donat

AU - Wood, W. Gibson

AU - Müller, Walter E.

AU - Eckert, Gunter P.

N1 - Funding Information: This work was supported in part by grants from the Hanna Bragard-Apfel Foundation, Alzheimer Forschung Initiative e.V. (AFI #07821 to D.K. and G.P.E, #06808 to T.D. and #08823 to G.P.E.) and the National Institutes of Health AG-23524, AG-18357 and the Department of Veterans Affairs to W.G.W. We thank Dr. Tobias Hartmann, Homburg, Germany for providing us with SH-SY5YAβPP695 cells and Dr. Paul M. Mathews, Nathan Kline Institute, Orangeburg, NY, for providing us with the mouse IgG C1/6.1 antibody. We also acknowledge the technical help of Dr. Eltahmash Israr, Claudia Jourdan and Anke Biczysko.

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N2 - Gradual changes in steady-state levels of beta amyloid peptides (Aβ) in brain are considered an initial step in the amyloid cascade hypothesis of Alzheimer's disease. Aβ is a product of the secretase cleavage of amyloid precursor protein (APP). There is evidence that the membrane lipid environment may modulate secretase activity and alters its function. Cleavage of APP strongly depends on membrane properties. Since Aβ perturbs cell membrane fluidity, the cell membrane may be the location where the neurotoxic cascade of Aβ is initiated. Therefore, we tested effects of oligomeric Aβ on membrane fluidity of whole living cells, the impact of exogenous and cellular Aβ on the processing of APP and the role of GM-1 ganglioside. We present evidence that oligoAβ(1-40) stimulates the amyloidogenic processing of APP by reducing membrane fluidity and complexing with GM-1 ganglioside. This dynamic action of Aβ may start a vicious circle, where endogenous Aβ stimulates its own production. Based on our novel findings, we propose that oligoAβ(1-40) accelerates the proteolytic cleavage of APP by decreasing membrane fluidity.

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The interaction of beta-amyloid protein with cellular membranes stimulates its own production

Abstract

Bibliographical note

Keywords

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