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

研究成果: Article査読

40 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)9304-9317
ページ数14
ジャーナルMolecular and Cellular Biology
25
21
DOI
出版ステータスPublished - 2005 11
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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