uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Cellular Polyamines Promote Amyloid-Beta (A beta) Peptide Fibrillation and Modulate the Aggregation Pathways
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
Show others and affiliations
2013 (English)In: ACS Chemical Neuroscience, ISSN 1948-7193, E-ISSN 1948-7193, Vol. 4, no 3, 454-462 p.Article in journal (Refereed) Published
Abstract [en]

The cellular polyamines spermine, spermidine, and their metabolic precursor putrescine, have long been associated with cell-growth, tumor-related gene regulations, and Alzheimer's disease. Here, we show by in vitro spectroscopy and AFM imaging, that these molecules promote aggregation of amyloid-beta (A beta) peptides into fibrils and modulate the aggregation pathways. NMR measurements showed that the three polyamines share a similar binding mode to monomeric A beta(1-40) peptide. Kinetic ThT studies showed that already very low polyamine concentrations promote amyloid formation: addition of 10 mu M spermine (normal intracellular concentration is similar to 1 mM) significantly decreased the lag and transition times of the aggregation process. Spermidine and putrescine additions yielded similar but weaker effects. CD measurements demonstrated that the three polyamines induce different aggregation pathways, involving different forms of induced secondary structure. This is supported by AFM images showing that the three polyamines induce A beta(1-40) aggregates with different morphologies. The results reinforce the notion that designing suitable ligands which modulate the aggregation of A beta peptides toward minimally toxic pathways may be a possible therapeutic strategy for Alzheimer's disease.

Place, publisher, year, edition, pages
2013. Vol. 4, no 3, 454-462 p.
Keyword [en]
Alzheimer's disease, amyloid-beta peptide, natural polyamines, protein-ligand binding, protein aggregation-pathway, peptide fibrillation
National Category
Medical and Health Sciences Natural Sciences
URN: urn:nbn:se:uu:diva-198621DOI: 10.1021/cn300170xISI: 000316594100011OAI: oai:DiVA.org:uu-198621DiVA: diva2:617232
Swedish National Infrastructure for Computing (SNIC), 001/12-15
Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2016-04-07

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Kamerlin, Lynn
By organisation
Department of Cell and Molecular BiologyComputational and Systems Biology
In the same journal
ACS Chemical Neuroscience
Medical and Health SciencesNatural Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 127 hits
ReferencesLink to record
Permanent link

Direct link