| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Outline of Final Research Achievements |
Mutations in proline-rich transmembrane protein 2 (PRRT2) are associated with several paroxysmal neurological diseases represented by paroxysmal kinesigenic dyskinesia (PKD), but physiological functions of PRRT2 and pathogenic mechanisms remain largely unclear as well as the causative brain regions and neuronal circuits. Here we generated Prrt2 knock-in (KI) mice harboring the most frequent PKD-related Prrt2 mutation and the mice showed that the Prrt2 mutation leads to an excessive activity-dependent dopaminergic transmission in striatum. Moreover, we found that PRRT2 regulates a dopamine transporter (DAT) activity in cultured neuroblastoma overexpressing both genes. Therefore, we considered that PRRT2 may contribute release and/or uptake of dopamine in the striatum and that loss of function of PRRT2 might cause PKD. Our findings showed that dopaminergic neurons in the basal ganglia could be a novel target for a treatment of PKD and several other neurological diseases with dyskinesia.
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