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Alzheimer Aβ peptides induce кB binding complexes containing C/EBPδ
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.ORCID iD: 0000-0002-0308-1964
Responsible organisation
(English)Manuscript (Other academic)
National Category
Biochemistry and Molecular Biology
URN: urn:nbn:se:su:diva-25296OAI: diva2:199365
Available from: 2008-09-04 Created: 2008-09-02 Last updated: 2016-01-29Bibliographically approved
In thesis
1. Alzheimer Aβ peptides induce dysregulation of C/EBP and NF-кB in glial cells
Open this publication in new window or tab >>Alzheimer Aβ peptides induce dysregulation of C/EBP and NF-кB in glial cells
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammation is believed to contribute to neurodegeneration in Alzheimer’s disease (AD). AD in turn is believed to be a consequence of accumulated amyloid-β (Aβ) peptides, that subsequently form senile plaques, due to imbalance between production and clearance of Aβ. Senile plaques are associated with dystrophic neurites, activated glia and various pro-inflammatory molecules. Microglia and astrocytes become activated to repair damage and kill intruders. There is a dramatic change in gene expression upon activation leading to production of pro-inflammatory and cytotoxic molecules. However in AD, glial cells fail to eliminate the disturbing agent and inflammation becomes chronic. Gene expression of putatively neurotoxic factors is under the control of various transcription factors. To find ways to increase beneficial effects of inflammation (phagocytosis of plaques) and dampen detrimental effects (production of neurotoxic molecules) it is important to understand how transcription factors responsible for these processes are regulated.

The aim of this thesis was to investigate the effects of Aβ on C/EBP and NF-кB transcription factors in mixed primary glial cultures activated by inflammatory mediators. In addition, we investigated the possibility to block effects downstream of the кB element with an NF-кB decoy coupled to a cell-penetrating peptide (CPP).

Our results show that Aβ peptides blocked interleukin (IL)-1β induced activation of C/EBPβ and C/EBPδ whereas the effect on NF-кB was the opposite. Furthermore, we observed C/EBPδ containing complexes binding to the кB element only in the presence of Aβ peptides and IL-1β. In addition, NF-кB p65 was found in complexes binding to the C/EBP site under all conditions. Lastly, we could block IL-6 mRNA expression levels to 50% using a CPP-NF-кB decoy. In summary, dysregulation of C/EBPβ, C/EBPδ and NF-кB in response to Aβ peptides and inflammatory mediators support that the normal inflammatory response is disturbed in AD.

Place, publisher, year, edition, pages
Stockholm: Institutionen för neurokemi, 2008. 124 p.
Alzheimer's disease, amyloid-β, astrocytes, C/EBP, glia, microglia, neuroinflammation, NF-кB
National Category
Research subject
Neurochemistry and Neurotoxicology
urn:nbn:se:su:diva-7968 (URN)978-91-7155-682-0 (ISBN)
Public defence
2008-09-26, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 12 A, Stockholm, 10:00
Available from: 2008-09-04 Created: 2008-09-02 Last updated: 2011-09-21Bibliographically approved

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Iverfeldt, Kerstin
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