A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers.

Autor:	Cataldi R; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Chia S; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Pisani K; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Ruggeri FS; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Xu CK; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Šneideris T; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.; Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, 10257, Lithuania., Perni M; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Sarwat S; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Joshi P; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Kumita JR; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Linse S; Department of Biochemistry and Structural Biology, Center for Molecular Protein Science, Lund University, Lund, Sweden., Habchi J; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Knowles TPJ; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK.; Cavendish Laboratory, University of Cambridge, Cambridge, CB3 0HE, UK., Mannini B; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. bm475@cam.ac.uk., Dobson CM; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK., Vendruscolo M; Centre for Misfolding Diseases, Department of Chemistry, University of Cambridge, Cambridge, CB2 1EW, UK. mv245@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	Communications biology [Commun Biol] 2021 Jan 04; Vol. 4 (1), pp. 19. Date of Electronic Publication: 2021 Jan 04.
DOI:	10.1038/s42003-020-01490-3
Abstrakt:	Aberrant soluble oligomers formed by the amyloid-β peptide (Aβ) are major pathogenic agents in the onset and progression of Alzheimer's disease. A variety of biomolecules can influence the formation of these oligomers in the brain, although their mechanisms of action are still largely unknown. Here, we studied the effects on Aβ aggregation of DOPAL, a reactive catecholaldehyde intermediate of dopamine metabolism. We found that DOPAL is able to stabilize Aβ oligomeric species, including dimers and trimers, that exert toxic effects on human neuroblastoma cells, in particular increasing cytosolic calcium levels and promoting the generation of reactive oxygen species. These results reveal an interplay between Aβ aggregation and key biochemical processes regulating cellular homeostasis in the brain.
Databáze:	MEDLINE
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