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 Koyama, Yoshiko Kita, Takako Niikura, Sadakazu Aiso, Dale E. Bredesen, Masaaki Matsuoka, Ikuo Nishimoto

Research output: Contribution to journalArticle

53 Citations (Scopus)

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

Fingerprint

Nerve Growth Factor Receptor
Cell death
Amyloid
Cell Death
Apoptosis
Peptides
NADPH Oxidase
Caspases
Heterotrimeric GTP-Binding Proteins
Death Domain
Hybrid Cells
Amyloid Plaques
Insulin-Like Growth Factor I
Toxicity
Alzheimer Disease
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-β peptides via p75NTR/PLAIDD. / Hashimoto, Yuichi; Kaneko, Yuka; Tsukamoto, Emi; Frankowski, Harald; Koyama, Keisuke; Kita, Yoshiko; Niikura, Takako; Aiso, Sadakazu; Bredesen, Dale E.; Matsuoka, Masaaki; Nishimoto, Ikuo.

In: Journal of Neurochemistry, Vol. 90, No. 3, 08.2004, p. 549-558.

Research output: Contribution to journalArticle

Hashimoto, Y, Kaneko, Y, Tsukamoto, E, Frankowski, H, Koyama, K, Kita, Y, Niikura, T, Aiso, S, Bredesen, DE, Matsuoka, M & Nishimoto, I 2004, 'Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-β peptides via p75NTR/PLAIDD', Journal of Neurochemistry, vol. 90, no. 3, pp. 549-558. https://doi.org/10.1111/j.1471-4159.2004.02513.x
Hashimoto, Yuichi ; Kaneko, Yuka ; Tsukamoto, Emi ; Frankowski, Harald ; Koyama, Keisuke ; Kita, Yoshiko ; Niikura, Takako ; Aiso, Sadakazu ; Bredesen, Dale E. ; Matsuoka, Masaaki ; Nishimoto, Ikuo. / Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid-β peptides via p75NTR/PLAIDD. In: Journal of Neurochemistry. 2004 ; Vol. 90, No. 3. pp. 549-558.
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