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Molecular characterization of neurohybrid cell death induced by Alzheimer's amyloid‐β peptides via p75NTR/PLAIDD
Author(s) -
Hashimoto Yuichi,
Kaneko Yuka,
Tsukamoto Emi,
Frankowski Harald,
Kouyama Keisuke,
Kita Yoshiko,
Niikura Takako,
Aiso Sadakazu,
Bredesen Dale E.,
Matsuoka Masaaki,
Nishimoto Ikuo
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02513.x
Subject(s) - neurotoxicity , microbiology and biotechnology , low affinity nerve growth factor receptor , senile plaques , programmed cell death , caspase , chemistry , extracellular , nadph oxidase , apoptosis , neurotrophin , receptor , biology , alzheimer's disease , biochemistry , reactive oxygen species , medicine , toxicity , disease , organic chemistry
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.