title: The effect of tachykinin neuropeptides on amyloid β aggregation.
abstract: A hallmark of Alzheimer's disease is production of amyloid β peptides resulting from aberrant cleavage of the amyloid precursor protein. Amyloid β assembles into fibrils under physiological conditions, through formation of neurotoxic intermediate oligomers. Tachykinin peptides are known to affect amyloid β neurotoxicity in cells. To understand the mechanism of this effect, we studied how tachykinins affect Aβ(1-40) aggregation in vitro. Fibrils grown in the presence of tachykinins exhibited reduced thioflavin T (ThT) fluorescence, while their morphology, observed in transmission electron microscopy (TEM), did not alter. Cross linking studies revealed that the distribution of low molecular weight species was not affected by tachykinins. Our results suggest that there may be a specific interaction between tachykinins and Aβ(1-40) that allows them to co-assemble. This effect may explain the reduction of Aβ(1-40) neurotoxicity in cells treated with tachykinins.
authors.affiliation: The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 91904, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Flashner
authors.forename: Uri
authors.initials: U
authors.lastname: Raviv
authors.forename: Assaf
authors.initials: A
authors.lastname: Friedler
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000682:Amyloid / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D052160:Benzothiazoles; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D015320:Tachykinins / Q000737:chemistry* / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D015320:Tachykinins; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T