Cellular Polyamines Promote Amyloid-Beta (A beta) Peptide Fibrillation and Modulate the Aggregation Pathways

Luo, Jinghui (author)

Yu, Chien-Hung (author)

Yu, Huixin (author)

Borstnar, Rok (author): Uppsala universitet,Institutionen för cell- och molekylärbiologi

Gräslund, Astrid (author): Stockholms universitet,Institutionen för biokemi och biofysik

Abrahams, Jan Pieter (author)

Wärmländer, Sebastian K. T. S. (author): Stockholms universitet,Institutionen för biokemi och biofysik

(creator_code:org_t)

2013-01-16
2013
English.
In: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 4:3, s. 454-462

Related links:: https://europepmc.or...; show more...; https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; show less...

Abstract Subject headings

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.

By the author/editor: Luo, Jinghui; Yu, Chien-Hung; Yu, Huixin; Borstnar, Rok; Kamerlin, Lynn; Gräslund, Astrid; show more...; Abrahams, Jan Pi ...; Wärmländer, Seba ...; show less...

About the subject

NATURAL SCIENCES: NATURAL SCIENCES; and Biological Scien ...; and Biochemistry and ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.