A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • Rodrigo Cataldi
  • Sean Chia
  • Katarina Pisani
  • Francesco S. Ruggeri
  • Catherine K. Xu
  • Tomas Šneideris
  • Michele Perni
  • Sunehera Sarwat
  • Priyanka Joshi
  • Janet R. Kumita
  • Sara Linse
  • Johnny Habchi
  • Tuomas P.J. Knowles
  • Benedetta Mannini
  • Christopher M. Dobson
  • Michele Vendruscolo
Organisations
External organisations
  • University of Cambridge
  • Vilnius University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
  • Neurosciences
Original languageEnglish
Article number19
JournalCommunications Biology
Volume4
Issue number1
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes