Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice

Sylvain Lesné, Fabian Docagne, Cecília Gabriel, Géraldine Liot, Debomoy Lahiri, Luc Buée, Laurent Plawinski, André Delacourte, Eric T. MacKenzie, Alain Buisson, Denis Vivien

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Abstract

Accumulation of the amyloid-β peptide (Aβ) in the brain is crucial for development of Alzheimer's disease. Expression of transforming growth factor-β1 (TGF-β1), an immunosuppressive cytokine, has been correlated in vivo with Aβ accumulation in transgenic mice and recently with Aβ clearance by activated microglia. Here, we demonstrate that TGF-β1 drives the production of Aβ40/42 by astrocytes leading to Aβ production in TGF-β1 transgenic mice. First, TGF-β1 induces the overexpression of the amyloid precursor protein (APP) in astrocytes but not in neurons, involving a highly conserved TGF-β1-responsive element in the 5′-untranslated region (+54/+74) of the APP promoter. Second, we demonstrated an increased release of soluble APP-β which led to TGF-β1-induced Aβ generation in both murine and human astrocytes. These results demonstrate that TGF-β1 potentiates Aβ production in human astrocytes and may enhance the formation of plaques burden in the brain of Alzheimer's disease patients.

Original languageEnglish
Pages (from-to)18408-18418
Number of pages11
JournalJournal of Biological Chemistry
Volume278
Issue number20
DOIs
StatePublished - May 16 2003

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Transforming Growth Factors
Amyloid
Astrocytes
Transgenic Mice
Amyloid beta-Protein Precursor
Brain
Alzheimer Disease
5' Untranslated Regions
Microglia
Brain Diseases
Immunosuppressive Agents
Neurons
Cytokines

ASJC Scopus subject areas

  • Biochemistry

Cite this

Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice. / Lesné, Sylvain; Docagne, Fabian; Gabriel, Cecília; Liot, Géraldine; Lahiri, Debomoy; Buée, Luc; Plawinski, Laurent; Delacourte, André; MacKenzie, Eric T.; Buisson, Alain; Vivien, Denis.

In: Journal of Biological Chemistry, Vol. 278, No. 20, 16.05.2003, p. 18408-18418.

Research output: Contribution to journalArticle

Lesné, S, Docagne, F, Gabriel, C, Liot, G, Lahiri, D, Buée, L, Plawinski, L, Delacourte, A, MacKenzie, ET, Buisson, A & Vivien, D 2003, 'Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice', Journal of Biological Chemistry, vol. 278, no. 20, pp. 18408-18418. https://doi.org/10.1074/jbc.M300819200
Lesné, Sylvain ; Docagne, Fabian ; Gabriel, Cecília ; Liot, Géraldine ; Lahiri, Debomoy ; Buée, Luc ; Plawinski, Laurent ; Delacourte, André ; MacKenzie, Eric T. ; Buisson, Alain ; Vivien, Denis. / Transforming growth factor-β1 potentiates amyloid-β generation in astrocytes and in transgenic mice. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 20. pp. 18408-18418.
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