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

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)627-636
Number of pages10
JournalJournal of Neuroscience Research
Volume73
Issue number5
DOIs
Publication statusPublished - 2003 Sep 1

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Nerve Growth Factor Receptor
Hybrid Cells
Poisons
Pertussis Toxin
Amyloid
Alzheimer Disease
Cell Death
Nerve Growth Factor Receptors
Peptides
Caspase 9
NADPH Oxidase
Protein Subunits
Fibroblast Growth Factor 2
Insulin-Like Growth Factor I
GTP-Binding Proteins
Caspase 3
Cause of Death
Pathology
Neurons
Brain

Keywords

  • Caspase
  • G
  • JNK
  • L401K mutant
  • NADPH oxidase

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Characterization of the toxic mechanism triggered by Alzheimer's amyloid-β peptides via p75 neurotrophin receptor in neuronal hybrid cells. / Tsukamoto, Emi; Hashimoto, Yuichi; Kanekura, Kohsuke; Niikura, Takako; Aiso, Sadakazu; Nishimoto, Ikuo.

In: Journal of Neuroscience Research, Vol. 73, No. 5, 01.09.2003, p. 627-636.

Research output: Contribution to journalArticle

Tsukamoto, Emi ; Hashimoto, Yuichi ; Kanekura, Kohsuke ; Niikura, Takako ; Aiso, Sadakazu ; Nishimoto, Ikuo. / Characterization of the toxic mechanism triggered by Alzheimer's amyloid-β peptides via p75 neurotrophin receptor in neuronal hybrid cells. In: Journal of Neuroscience Research. 2003 ; Vol. 73, No. 5. pp. 627-636.
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