Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-β peptides via p75NTR/PLAIDD

Yuichi Hashimoto, Yuka Kaneko, Emi Tsukamoto, Harald Frankowski, Keisuke Kouyama, Yoshiko Kita, Takako Niikura, Sadakazu Aiso, Dale E. Bredesen, Masaaki Matsuoka, Ikuo Nishimoto

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Abstract

One of the most important pathological features of Alzheimer's disease (AD) is extracellular senile plaques, whose major component is amyloid-β peptides (Aβ). Aβ binds to the extracellular domain of p75NTR (p75 neurotrophin receptor) and induces neuronal cell death. We investigated the molecular mechanism of Aβ-induced neurotoxicity in detail from the standpoint of interaction between p75NTR and its recently identified relative, PLAIDD (p75-like apoptosis-inducing death domain). Using F11 neuronal hybrid cells, we demonstrate that there are two distinct pathways for Aβ-induced toxicity mediated by p75NTR. One pathway that has been previously elucidated, is mediated by p75NTR, Go, JNK, NADPH oxidase and caspase3-related caspases. We found that PLAIDD and Gi proteins, heterotrimeric G proteins, are involved in the alternative Aβ-induced neurotoxicity mediated by p75NTR. The alternative pathway triggered by Aβ is thus mediated by p75NTR, PLAIDD, Gi, JNK, NADPH oxidase and caspase3-related caspases. In addition, we found that HN, ADNF, IGF-I, or bFGF inhibits both pathways of Aβ-induced neurotoxicity mediated by p75NTR.

Original languageEnglish
Pages (from-to)549-558
Number of pages10
JournalJournal of Neurochemistry
Volume90
Issue number3
DOIs
Publication statusPublished - 2004 Aug 1

Keywords

  • Alzheimer's disease
  • Amyloid-β peptides
  • Gi/o proteins
  • Humanin
  • P75 neurotrophin receptor
  • PLAIDD

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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    Hashimoto, Y., Kaneko, Y., Tsukamoto, E., Frankowski, H., Kouyama, K., Kita, Y., Niikura, T., Aiso, S., Bredesen, D. E., Matsuoka, M., & Nishimoto, I. (2004). Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-β peptides via p75NTR/PLAIDD. Journal of Neurochemistry, 90(3), 549-558. https://doi.org/10.1111/j.1471-4159.2004.02513.x