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PMID: 9122249 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Transcription factor NF-kappaB is activated in primary neurons by amyloid beta peptides and in neurons surrounding early plaques from patients with Alzheimer disease.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 6 ·1997-03-18 ·Pages 2642-7

Kaltschmidt B, Uherek M, Volk B, Baeuerle PA, Kaltschmidt C

Abstract

Amyloid beta peptide (A beta)-containing plaques are a hallmark of Alzheimer disease. Here, we show that the neurotoxic A beta, a major plaque component, is a potent activator of the transcription factor NF-kappaB in primary neurons. This activation required reactive oxygen intermediates as messengers because an antioxidant prevented A beta-induced NF-kappaB activation. Maximal activation of NF-kappaB was found with 0.1 microM A beta-(1-40) and 0.1 microM A beta-(25-35) fragments, making a role for NF-kappaB in neuroprotection feasible. Using an activity-specific mAb for the p65 NF-kappaB subunit, activation of NF-kappaB also was observed in neurons and astroglia of brain sections from Alzheimer disease patients. Activated NF-kappaB 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 A beta-induced activation of NF-kappaB, a potent immediate-early transcriptional regulator of numerous proinflammatory genes.

MeSH Terms
Alzheimer Disease/metabolism,pathology Amyloid beta-Peptides/pharmacology Animals Antioxidants/pharmacology Astrocytes/metabolism,pathology Catalase/pharmacology Cells, Cultured Cerebellum/metabolism,pathology Humans NF-kappa B/biosynthesis Neurons/drug effects,metabolism,pathology Peptide Fragments/pharmacology Proline/analogs & derivatives,pharmacology Rats Rats, Wistar Thiocarbamates/pharmacology
Chemicals
Amyloid beta-Peptides Antioxidants NF-kappa B Peptide Fragments Thiocarbamates amyloid beta-protein (1-40) amyloid beta-protein (25-35) prolinedithiocarbamate Proline Catalase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kaltschmidt B
Institute of Biochemistry and Molecular Biology, Albert-Ludwigs-University, Freiburg, Germany. kaltschm@ruf.uni-freiburg.de
Uherek M
Volk B
Baeuerle P A
Kaltschmidt C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.6.2642
Email
kaltschm@ruf.uni-freiburg.de
Published
1997-03-18
Pages
2642-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC20142
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.94.6.2642 PMC Full Text View journal details
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