2019 Fiscal Year Research-status Report
Pyridoxamine could be a candidate drug for Parkinson`s disease: Mechanistic study to reduce dopamine-induced toxicity
| Project/Area Number |
19K07187
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| Research Institution | Tohoku University |
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Principal Investigator |
李 宣和 東北大学, 薬学研究科, 准教授 (60519776)
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| Co-Investigator(Kenkyū-buntansha) |
大江 知行 東北大学, 薬学研究科, 教授 (10203712)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | Pyridoxamine / Dopamine / Parkinson`s disease / Oxidative stress |
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| Outline of Annual Research Achievements |
Characterization of a pyridoxamine (PM)-dopamine (DA) adduct:
1. In the reaction of DA and PM, the (pyridoxal) PL-DA adduct was formed together with PL. The adduct corresponded to PL+DA-H2O was also produced in the reaction of DA and PL. Its structure was characterized to be a 1-[3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl-1,2,3,4-tetrahydroisoquinoline-6,7-diol formed through a Schiff base by MS/MS, UV, and NMR analyses.
2. Based on the results from the reaction of DA analogs and PM, the mechanism for the formation of PL-DA adduct was proposed. Thus, DA initially oxidizes to DA quinone (DAQ), which reacts with PM to produce PL after hydrolysis. PL then reacts with DA to form PL-DA adduct.
3. As the PM concentration increased, dose-dependent elevation of a PL-DA adduct was observed.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
As planned, DA was allowed to react with PM and the adduct (PL+DA-H2O) was characterized by MS/MS, UV, and NMR analyses. The mechanism for the formation of adduct was also proposed based on the reaction of DA analogs and PM. Dose-dependent elevation of a PL-DA adduct was observed. Therefore, PM could inhibit DA-induced neurotoxicity by directly scavenging DAQ.
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| Strategy for Future Research Activity |
Investigation of the inhibition effects of PM:
1. Cysteine will be allowed to react with DA in the presence of PM.
2. Time- and concentration-dependent inhibition effects of PM will be investigated by monitoring the formations of 5S-cysteinyl-DA and a PM-DA adduct.
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