The dopamine receptor agonist apomorphine stabilizes neurotoxic α-synuclein oligomers.
Parkinson´s disease
apomorphine
dopamine
neurotoxicity
oligomer
α-synuclein
Journal
FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
13
11
2021
received:
26
10
2021
accepted:
10
12
2021
pubmed:
21
12
2021
medline:
3
3
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
The misfolding and aggregation of the protein α-synuclein (aSyn) into potentially neurotoxic oligomers is believed to play a pivotal role in the neuropathogenesis of Parkinson's disease (PD). Herein, we explore how apomorphine (Apo), a nonselective dopamine D1 and D2 receptor agonist utilized in the therapy for PD, affects the aggregation and toxicity of aSyn in vitro. Our data indicated that Apo inhibits aSyn fibrillation leading to the formation of large oligomeric species (Apo-aSyn-O), which exhibit remarkable toxicity in mesencephalic dopaminergic neurons in primary cultures. Interestingly, purified Apo-aSyn-O, even at very low concentrations, seems to be capable of converting unmodified aSyn monomer into neurotoxic species. Collectively, our findings warn for a possible dangerous effect of Apo on aSyn misfolding/aggregation pathway.
Identifiants
pubmed: 34928512
doi: 10.1002/1873-3468.14263
pmc: PMC8972942
mid: NIHMS1788207
doi:
Substances chimiques
SNCA protein, human
0
alpha-Synuclein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
309-322Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM136686
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG019391
Pays : United States
Informations de copyright
© 2021 Federation of European Biochemical Societies.
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