β-amyloid binds to p75NTR and activates NFκB in human neuroblastoma cells

• Published in: Journal of neuroscience research Vol. 54; no. 6; pp. 798 - 804
• Main Authors: Kuner, Pascal, Schubenel, Robert, Hertel, Cornelia
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 15.12.1998
• Subjects: Alzheimer's disease; apoptosis; neurotrophin; p75NTR; β-amyloid
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/(SICI)1097-4547(19981215)54:6<798::AID-JNR7>3.0.CO;2-T

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 (p75NTR), a nonselective neurotrophin receptor belonging to the death receptor family, has been reported. p75NTR expression has been described to correlate with β‐amyloid sensitivity in vivo and in vitro, suggesting a possible role for p75NTR as a receptor for Aβ. Here we used a human neuroblastoma cell line to investigate the involvement of p75NTR in Aβ‐induced cell death. Aβ peptides were found to bind to p75NTR resulting in activation of NFκB in a time‐ and dose‐dependent manner. Blocking the interaction of Aβ with p75NTR 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 p75NTR 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.