A Direct Interaction between Transforming Growth Factor (TGF)-βs and Amyloid-β Protein Affects Fibrillogenesis in a TGF-β Receptor-independent Manner

From National Research Council Canada

DOI	Resolve DOI: https://doi.org/10.1074/jbc.M304080200
Author	Search for: Mousseau, Darrell D.¹; Search for: Chapelsky, Sarah¹; Search for: De Crescenzo, Gregory¹; Search for: Kirkitadze, Marina D.; Search for: Magoon, Joanne¹; Search for: Inoue, Sadayuki; Search for: Teplow, David B.; Search for: O'Connor-McCourt, Maureen D.¹
Name affiliation	National Research Council Canada. NRC Biotechnology Research Institute
Format	Text
Type	Article
Journal title	The Journal of Biological Chemistry
ISSN	0021-9258 1083-351X
Volume	278
Issue	40
Pages	38715–38722
Subject	pharmaceutical
Abstract	Transforming growth factor-β (TGF-β) receptor-mediated signaling has been proposed to mediate both the beneficial and deleterious roles for this cytokine in amyloid-β protein (Aβ) function. In order to assess receptor dependence of these events, we used PC12 cell cultures, which are devoid of TGF-β receptors. Surprisingly, TGF-β potentiated the neurotoxic effects of the 40-residue Aβ peptide, Aβ-(1–40), in this model suggesting that there may be a direct, receptor-independent interaction between TGF-β and Aβ-(1–40). Surface plasmon resonance confirmed that TGF-β binds with high affinity directly to Aβ-(1–40) and electron microscopy revealed that TGF-β enhances Aβ-(1–40) oligomerization. Immunohistochemical examination of mouse brain revealed that hippocampal CA1 and dentate gyrus, two regions classically associated with Aβ-mediated pathology, lack TGF-β Type I receptor immunoreactivity, thus indicating that TGF-β receptor-mediated signaling would not be favored in these regions. Our observations not only provide for a unique, receptor-independent mechanism of action for TGF-β, but also help to reconcile the literature interpreting the role of TGF-β in Aβ function. These data support a critical etiological role for this mechanism in neuropathological amyloidoses.
Publication date	2003-07-16
Publisher	American Society for Biochemistry and Molecular Biology
Language	English
Peer reviewed	Yes
NRC number	NRC-BRI-46165
NPARC number	3540136
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Record identifier	c54f3713-33e9-468c-aac2-84fe618d156e
Record created	2009-03-01
Record modified	2020-02-19

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Date modified:: 2020-02-27