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A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers

Cataldi, Rodrigo ; Chia, Sean ; Pisani, Katarina ; Ruggeri, Francesco S. ; Xu, Catherine K. ; Šneideris, Tomas ; Perni, Michele ; Sarwat, Sunehera ; Joshi, Priyanka and Kumita, Janet R. , et al. (2021) In Communications Biology 4(1).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Communications Biology
volume
4
issue
1
article number
19
publisher
Nature Research
external identifiers
  • scopus:85098622368
  • pmid:33398040
ISSN
2399-3642
DOI
10.1038/s42003-020-01490-3
language
English
LU publication?
yes
id
3ef8a5b9-b63c-4fce-b39a-8b3335645b5c
date added to LUP
2021-01-12 12:15:58
date last changed
2021-04-13 03:11:00
@article{3ef8a5b9-b63c-4fce-b39a-8b3335645b5c,
  abstract     = {<p>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.</p>},
  author       = {Cataldi, Rodrigo and Chia, Sean and Pisani, Katarina and Ruggeri, Francesco S. and Xu, Catherine K. and Šneideris, Tomas and Perni, Michele and Sarwat, Sunehera and Joshi, Priyanka and Kumita, Janet R. and Linse, Sara and Habchi, Johnny and Knowles, Tuomas P.J. and Mannini, Benedetta and Dobson, Christopher M. and Vendruscolo, Michele},
  issn         = {2399-3642},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Research},
  series       = {Communications Biology},
  title        = {A dopamine metabolite stabilizes neurotoxic amyloid-β oligomers},
  url          = {http://dx.doi.org/10.1038/s42003-020-01490-3},
  doi          = {10.1038/s42003-020-01490-3},
  volume       = {4},
  year         = {2021},
}