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β‐amyloid binds to p75 NTR and activates NFκB in human neuroblastoma cells
Author(s) -
Kuner Pascal,
Schubenel Robert,
Hertel Cornelia
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19981215)54:6<798::aid-jnr7>3.0.co;2-t
Subject(s) - nf κb , neuroblastoma , amyloid (mycology) , microbiology and biotechnology , chemistry , cancer research , biology , cell culture , signal transduction , genetics , inorganic chemistry
Amyloid β peptide (Aβ), a proteolytic fragment of the amyloid precursor protein (APP), is a major component of the plaques found in the brain of Alzheimer's disease (AD) patients. These plaques are thought to cause the observed loss of cholinergic neurons in the basal forebrain of AD patients. In these neurons, particularly those of the nucleus basalis of Meynert, an up‐regulation of 75kD‐neurotrophin receptor (p75 NTR ), a nonselective neurotrophin receptor belonging to the death receptor family, has been reported. p75 NTR expression has been described to correlate with β‐amyloid sensitivity in vivo and in vitro, suggesting a possible role for p75 NTR as a receptor for Aβ. Here we used a human neuroblastoma cell line to investigate the involvement of p75 NTR in Aβ‐induced cell death. Aβ peptides were found to bind to p75 NTR resulting in activation of NFκB in a time‐ and dose‐dependent manner. Blocking the interaction of Aβ with p75 NTR using NGF or inhibition of NFκB activation by curcumin or NFκB SN50 attenuated or abolished Aβ‐induced apoptotic cell death. The present results suggest that p75 NTR might be a death receptor for Aβ, thus being a possible drug target for treatment of AD. J. Neurosci. Res. 54:798–804, 1998. © 1998 Wiley‐Liss, Inc.