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Detergent-like interaction of Congo red with the amyloid beta peptide
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
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2010 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 49, no 7, 1358-1360 p.Article in journal (Refereed) Published
Abstract [en]

Accumulating evidence links prefibrillar oligomeric species of the amyloid beta peptide (Abeta) to cellular toxicity in Alzheimer's disease, potentially via disruption of biological membranes. Congo red (CR) affects protein aggregation. It is known to self-associate into micelle-like assemblies but still reduces the toxicity of Abeta aggregates in cell cultures and model organisms. We show here that CR interacts with Abeta(1-40) in a manner similar to that of anionic detergents. Although CR promotes beta sheet formation and peptide aggregation, it may also solubilize toxic protein species, making them less harmful to critical cellular components and thereby reducing amyloid toxicity.

Place, publisher, year, edition, pages
2010. Vol. 49, no 7, 1358-1360 p.
Keyword [en]
Alzheimer's disease, amyloid beta peptide, Congo red
National Category
Chemical Sciences Biochemistry and Molecular Biology
Research subject
URN: urn:nbn:se:su:diva-51710DOI: 10.1021/bi902005tPubMedID: 20070125OAI: diva2:385734
Available from: 2011-01-12 Created: 2011-01-12 Last updated: 2011-08-19Bibliographically approved
In thesis
1. NMR studies on interactions between the amyloid β peptide and selected molecules
Open this publication in new window or tab >>NMR studies on interactions between the amyloid β peptide and selected molecules
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Alzheimer’s disease is an incurable neurodegenerative disorder linked to the amyloid β (Aβ) peptide, a 38-43 residue peptide. The detailed molecular disease mechanism(s) is (are) unknown, but oligomeric Aβ structures are proposed to be involved.

In common for the papers in this thesis is interactions; interactions between Aβ(1-40) and selected molecules and metal ions. The purpose has been to find out more about the structural states that Aβ can adopt, in particular the β-sheet state, which probably is linked to the oligomeric structures. The methods used have been nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence spectroscopy using Thioflavin T (ThT).

Upon addition of SDS/LiDS detergent or Congo red (CR) to Aβ(1-40), the initial random coil/PII-helix state was transformed into β-sheet and, in the case of detergent, a final α-helical state. In contrast to SDS/LiDS and CR, the dimeric Affibody molecule locks monomeric Aβ(1-40) in a β-hairpin state. It was found that by truncating the flexible N-terminal end of the Affibody molecule its affinity to Aβ was improved. The aggregation of Aβ(1-40) was further studied in the presence of a β-cyclodextrin dimer by a kinetic assay using ThT. Although having a weak dissociation constant in the millimolar range, the β-cyclodextrin dimer modified the aggregation pathways of Aβ.

Finally Aβ(1-40) was studied in presence of Cu2+ and Zn2+ at physiological and low pH. Cu2+ was observed to maintain its specific binding to Aβ when decreasing the pH to 5.5 while Zn2+ behaved differently. This could be of importance in the Alzheimer’s disease brain in which the environment can become acidic due to inflammation.       

In conclusion the results show that Aβ(1-40) is very sensitive to its environment, responding by adopting different conformations and aggregating in aqueous solutions. The β-sheet state is induced by varying molecules with different properties, properties that govern the final Aβ state.

Place, publisher, year, edition, pages
Stockholm: Department of Biochemistry and Biophysics, Stockholm University, 2011. 59 p.
Amyloid β peptide, Alzheimer's disease, Aggregation, Oligomer, Amyloid, Interaction, Nuclear Magnetic Resonance Spectroscopy, Circular Dichroism Spectroscopy, Thioflavin T, Detergent, Congo red, Affibody, Cyclodextrin dimer, Metal ion
National Category
Chemical Sciences Biochemistry and Molecular Biology
Research subject
urn:nbn:se:su:diva-60346 (URN)978-91-7447-325-4 (ISBN)
Public defence
2011-10-07, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Manuscript. Paper 5: Manuscript.Available from: 2011-09-15 Created: 2011-08-15 Last updated: 2011-09-02Bibliographically approved

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Wahlström, AnnaGräslund, Astrid
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