DOPAnization of tyrosine in α-synuclein by tyrosine hydroxylase leads to the formation of oligomers.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 11 2022
12 11 2022
Historique:
received:
12
01
2022
accepted:
27
10
2022
pubmed:
13
11
2022
medline:
16
11
2022
entrez:
12
11
2022
Statut:
epublish
Résumé
Parkinson's disease is a progressive neurodegenerative disorder characterized by the preferential loss of tyrosine hydroxylase (TH)-expressing dopaminergic neurons in the substantia nigra. Although the abnormal accumulation and aggregation of α-synuclein have been implicated in the pathogenesis of Parkinson's disease, the underlying mechanisms remain largely elusive. Here, we found that TH converts Tyr136 in α-synuclein into dihydroxyphenylalanine (DOPA; Y136DOPA) through mass spectrometric analysis. Y136DOPA modification was clearly detected by a specific antibody in the dopaminergic neurons of α-synuclein-overexpressing mice as well as human α-synucleinopathies. Furthermore, dopanized α-synuclein tended to form oligomers rather than large fibril aggregates and significantly enhanced neurotoxicity. Our findings suggest that the dopanization of α-synuclein by TH may contribute to oligomer and/or seed formation causing neurodegeneration with the potential to shed light on the pathogenesis of Parkinson's disease.
Identifiants
pubmed: 36371400
doi: 10.1038/s41467-022-34555-4
pii: 10.1038/s41467-022-34555-4
pmc: PMC9653393
doi:
Substances chimiques
alpha-Synuclein
0
Tyrosine 3-Monooxygenase
EC 1.14.16.2
Tyrosine
42HK56048U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6880Informations de copyright
© 2022. The Author(s).
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