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

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 1
Externally publishedYes

Fingerprint

Nerve Growth Factor Receptor
Cell death
Amyloid
Apoptosis
Peptides
NADPH Oxidase
Caspases
Heterotrimeric GTP-Binding Proteins
Insulin-Like Growth Factor I
Toxicity
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

Hashimoto, Y., Kaneko, Y., Tsukamoto, E., Frankowski, H., Kouyama, K., Kita, Y., ... 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

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

In: Journal of Neurochemistry, Vol. 90, No. 3, 01.08.2004, p. 549-558.

Research output: Contribution to journalArticle

Hashimoto, Y, Kaneko, Y, Tsukamoto, E, Frankowski, H, Kouyama, 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 ; Kouyama, 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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