Reference - Detail
| RRC ID | 81378 |
|---|---|
| Author | Jin M, Matsumoto S, Ayaki T, Yamakado H, Taguchi T, Togawa N, Konno A, Hirai H, Nakajima H, Komai S, Ishida R, Chiba S, Takahashi R, Takao T, Hirotsune S. |
| Title | DOPAnization of tyrosine in α-synuclein by tyrosine hydroxylase leads to the formation of oligomers. |
| Journal | Nat Commun |
| Abstract |
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. |
| Volume | 13(1) |
| Pages | 6880 |
| Published | 2022-11-12 |
| DOI | 10.1038/s41467-022-34555-4 |
| PII | 10.1038/s41467-022-34555-4 |
| PMID | 36371400 |
| PMC | PMC9653393 |
| MeSH | Animals Dopaminergic Neurons / metabolism Humans Mice Parkinson Disease* / genetics Parkinson Disease* / pathology Substantia Nigra / metabolism Tyrosine Tyrosine 3-Monooxygenase / genetics Tyrosine 3-Monooxygenase / metabolism alpha-Synuclein* / genetics alpha-Synuclein* / metabolism |
| Resource | |
| DNA material | CSII-EF-MCS-IRES2-Venus (RDB04384) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393) |