2017 Fiscal Year Final Research Report
The chemical structural characterization of neuromelanins in human locus coeruleus and its aging process
| Project/Area Number |
15K09794
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | ニューロメラニン / ドーパミン / pro-oxidant activity / ROS / antioxidant / GSH |
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| Outline of Final Research Achievements |
Neuromelanin (NM), a dark brown pigment, is found in the Substantia Nigra (SN) in dopaminergic neurons and in the Locus coeruleus (LC) in norepinephrinergic neurons. This study shows that protein-bound dopamine (DA) conjugates formed during the production of NM have pro-oxidant activities that generate reactive oxygen species (ROS) and deplete reduced glutathione (GSH), the most important cellular antioxidant. Further, the results demonstrate that the DAquinone produced is bound to proteins via their SH groups and that the binding yield depends on the structural features of the protein. Binding via cysteine residues in proteins is formed by oxidation using redox-active metal ions as well as tyrosinase. These results suggest that protein-bound DA conjugates produced in the brain possess pro-oxidant activities, which may cause neurodegeneration due to the generation of ROS and the depletion of antioxidants.
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| Free Research Field |
有機化学
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