Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein

Yuichi Hashimoto, Tomohiro Chiba, Marina Yamada, Mikiro Nawa, Kohsuke Kanekura, Hiroaki Suzuki, Kenzo Terashita, Sadakazu Aiso, Ikuo Nishimoto, Masaaki Matsuoka

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

APP, amyloid β precursor protein, is linked to the onset of Alzheimer's disease (AD). We have here found that transforming growth factor β2 (TGFβ2), but not TGFβ1, binds to APP. The binding affinity of TGFβ2 to APP is lower than the binding affinity of TGFβ2 to the TGFβ receptor. On binding to APP, TGFβ2 activates an APP-mediated death pathway via heterotrimeric G protein Go, c-Jun N-terminal kinase, NADPH oxidase, and caspase 3 and/or related caspases. Overall degrees of TGFβ2-induced death are larger in cells expressing a familial AD-related mutant APP than in those expressing wild-type APP. Consequently, superphysiological concentrations of TGFβ2 induce neuronal death in primary cortical neurons, whose one allele of the APP gene is knocked in with the V642I mutation. Combined with the finding indicated by several earlier reports that both neural and glial expression of TGFβ2 was upregulated in AD brains, it is speculated that TGFβ2 may contribute to the development of AD-related neuronal cell death.

Original languageEnglish
Pages (from-to)9304-9317
Number of pages14
JournalMolecular and Cellular Biology
Volume25
Issue number21
DOIs
Publication statusPublished - 2005 Nov 1
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hashimoto, Y., Chiba, T., Yamada, M., Nawa, M., Kanekura, K., Suzuki, H., ... Matsuoka, M. (2005). Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein. Molecular and Cellular Biology, 25(21), 9304-9317. https://doi.org/10.1128/MCB.25.21.9304-9317.2005

Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein. / Hashimoto, Yuichi; Chiba, Tomohiro; Yamada, Marina; Nawa, Mikiro; Kanekura, Kohsuke; Suzuki, Hiroaki; Terashita, Kenzo; Aiso, Sadakazu; Nishimoto, Ikuo; Matsuoka, Masaaki.

In: Molecular and Cellular Biology, Vol. 25, No. 21, 01.11.2005, p. 9304-9317.

Research output: Contribution to journalArticle

Hashimoto, Y, Chiba, T, Yamada, M, Nawa, M, Kanekura, K, Suzuki, H, Terashita, K, Aiso, S, Nishimoto, I & Matsuoka, M 2005, 'Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein', Molecular and Cellular Biology, vol. 25, no. 21, pp. 9304-9317. https://doi.org/10.1128/MCB.25.21.9304-9317.2005
Hashimoto, Yuichi ; Chiba, Tomohiro ; Yamada, Marina ; Nawa, Mikiro ; Kanekura, Kohsuke ; Suzuki, Hiroaki ; Terashita, Kenzo ; Aiso, Sadakazu ; Nishimoto, Ikuo ; Matsuoka, Masaaki. / Transforming growth factor β2 is a neuronal death-inducing ligand for amyloid-β precursor protein. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 21. pp. 9304-9317.
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