| First Author | Jin M | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 6880 |
| PubMed ID | 36371400 | Mgi Jnum | J:337614 |
| Mgi Id | MGI:7386207 | Doi | 10.1038/s41467-022-34555-4 |
| Citation | Jin M, et al. (2022) DOPAnization of tyrosine in alpha-synuclein by tyrosine hydroxylase leads to the formation of oligomers. Nat Commun 13(1):6880 |
| abstractText | 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 alpha-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 alpha-synuclein into dihydroxyphenylalanine (DOPA; Y136DOPA) through mass spectrometric analysis. Y136DOPA modification was clearly detected by a specific antibody in the dopaminergic neurons of alpha-synuclein-overexpressing mice as well as human alpha-synucleinopathies. Furthermore, dopanized alpha-synuclein tended to form oligomers rather than large fibril aggregates and significantly enhanced neurotoxicity. Our findings suggest that the dopanization of alpha-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. |
