Characterization of the toxic mechanism triggered by Alzheimer's amyloid-β peptides via p75 neurotrophin receptor in neuronal hybrid cells

Emi Tsukamoto, Yuichi Hashimoto, Kohsuke Kanekura, Takako Niikura, Sadakazu Aiso, Ikuo Nishimoto

研究成果: Article査読

82 被引用数 (Scopus)

抄録

Neuronal pathology of the brain with Alzheimer's disease (AD) is characterized by numerous depositions of amyloid-β peptides (Aβ). Aβ binding to the 75-kDa neurotrophin receptor (p75NTR) causes neuronal cell death. Here we report that Aβ causes cell death in neuronal hybrid cells transfected with p75NTR, but not in non-transfected cells, and that p75NTRL401K cannot mediate Aβ neurotoxicity. We analyzed the cytotoxic pathway by transfecting pertussis toxin (PTX)-resistant G protein α subunits in the presence of PTX and identified that Gα o, but not Gαi, proteins are involved in p75NTR-mediated Aβ neurotoxicity. Further investigation suggested that Aβ neurotoxicity via p75NTR involved JNK, NADPH oxidase, and caspases-9/3 and was inhibited by activity-dependent neurotrophic factor, insulin-like growth factor-I, basic fibroblast growth factor, and Humanin, as observed in primary neuron cultures. Understanding the Aβ neurotoxic mechanism would contribute significantly to the development of anti-AD therapies.

本文言語English
ページ(範囲)627-636
ページ数10
ジャーナルJournal of neuroscience research
73
5
DOI
出版ステータスPublished - 2003 9月 1

ASJC Scopus subject areas

  • 細胞および分子神経科学

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