Details

Autor(en) / Beteiligte

• Kaltschmidt, Barbara
• Uherek, Martin
• Volk, Benedikt
• Baeuerle, Patrick A.
• Kaltschmidt, Christian

Titel

Transcription Factor NF-κ B is Activated in Primary Neurons by Amyloid β Peptides and in Neurons Surrounding Early Plaques from Patients with Alzheimer Disease

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1997-03, Vol.94 (6), p.2642-2647

Ort / Verlag

National Academy of Sciences of the United States of America

Erscheinungsjahr

1997

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Amyloid β peptide (Aβ )-containing plaques are a hallmark of Alzheimer disease. Here, we show that the neurotoxic Aβ , a major plaque component, is a potent activator of the transcription factor NF-κ B in primary neurons. This activation required reactive oxygen intermediates as messengers because an antioxidant prevented Aβ -induced NF-κ B activation. Maximal activation of NF-κ B was found with 0.1 μ M Aβ -(1-40) and 0.1 μ M Aβ -(25-35) fragments, making a role for NF-κ B in neuroprotection feasible. Using an activity-specific mAb for the p65 NF-κ B subunit, activation of NF-κ B also was observed in neurons and astroglia of brain sections from Alzheimer disease patients. Activated NF-κ B was restricted to cells in the close vicinity of early plaques. Our data suggest that the aberrant gene expression in diseased nervous tissue is at least in part due to Aβ -induced activation of NF-κ B, a potent immediate--early transcriptional regulator of numerous proinflammatory genes.