| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Tetrahydrobiopterin (BH4) is a cofactor required for the biosynthesis of neurotransmitters involved in the nociceptive neurotransmission. BH4 de novo synthesis is led by GTP cyclohydrolase 1 (GCH1) which is the first and rate-limiting enzyme in that synthetic pathway. In the other hand, BH4 salvage pathway is linked to the folate metabolic pathway via methyltetrahydrofolate reductase. Since GCH1, MTHFR are known as pain marker and availability in BH4 is linked to chronic pain, we evaluate the potential of those metabolic pathways in pain. Several approaches were used to leverage BH4 availability in vitro. The involvement of these metabolic pathways was assessed in animal model of visceral pain. Evolutional conservation of these metabolic pathways were assessed in higher invertebrate animal model. Our observation suggested that those pathways are conserved among species and involved in availability of BH4 in pain. However their modulation using drugs is facing specificity challenges.
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