Journal Article

A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers

Šneideris Tomas, Mannini Benedetta, Cataldi, Rodrigo, Perni, Michele, Kumita, Janet R, Chia, Sean, Knowles Tuomas P J, Ruggeri, Francesco S, Joshi Priyanka, Pisani Katarina, Dobson, Christopher M, Habchi Johnny, Xu, Catherine K, Linse, Sara, Vendruscolo Michele, Sunehera, Sarwat

2021

Overview

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.Cataldi et al. investigates the impact of the dopamine derivative DOPAL on the Aβ peptide oligomer formation. They report that DOPAL promotes the formation of stable Aβ oligomers that exert toxicity on neuroblastoma cells by increasing cytosolic calcium levels and generating reactive oxygen species. This study connects Aβ aggregation with processes regulating cellular homeostasis in the brain.

• Publisher: Nature Publishing Group
• Subject: Alzheimer's disease / Biology / Calcium / Dopamine / Homeostasis / Metabolites / Neuroblastoma / Neuroblasts / Neurodegenerative diseases / Neurotoxicity / Peptides / Reactive oxygen species / Trimers / β-Amyloid