Pathogenic mechanisms of Parkinson's disease and movement disorders medicated by excess zinc influx into dopaminergic neuron and its rescue
| Project/Area Number |
17K08312
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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 |
Pharmacology in pharmacy
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| Research Institution | University of Shizuoka |
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Principal Investigator |
Tamano Haruna 静岡県立大学, 薬学部, 特任講師 (30322697)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | パーキンソン病 / 黒質 / 細胞外亜鉛 / 亜鉛毒性 / 活性酸素 / ドパミン作動性神経 / グルタミン酸興奮毒性 / 黒質神経変性 / パラコート / 細胞外亜鉛流入 / グルタミン酸受容体 / 加齢 / ドパミン作動性神経脱落 / 亜鉛イオン / 活性酸素種 / 細胞外グルタミン酸 / 亜鉛キレーター / 6-hydoxydopamine / 酸化ストレス / 黒質細胞死 / ドーパミンニューロン / 運動障害 / 神経疾患 / 亜鉛 |
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| Outline of Final Research Achievements |
Parkinson's disease (PD) is characterized by a selective loss of dopaminergic neurons in the substantia nigra in the brain. This study demonstrates a unique mechanism of nigral dopaminergic degeneration, in which rapid intracellular Zn2+dysregulation via reactive oxygen species (ROS) production causes PD in rats, which is induced by paraquart (PQ) and 6-hydroxydopamine (6-OHDA). ROS produced with PQ and 6-OHDA, which is retrogradely transported to presynaptic glutamatergic neuron terminals, activate TRPM2 cation channels and increase glutamate release, resulting in intracellular Zn2+ dysregulation in postsynaptic nigral dopaminergic neurons via rapid extracellular Zn2+ influx via AMPA receptor activation.
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| Academic Significance and Societal Importance of the Research Achievements |
活性酸素産生物質によって誘発されるパーキンソン病モデル動物を用いた本研究から、脳黒質ドパミンニューロン変性のメカニズムには、活性酸素によって誘導される黒質細胞外亜鉛の速やかな過剰流入による細胞内亜鉛毒性が重要であること、この亜鉛毒性を阻止することはパーキンソン病の予防・阻止につかながることが示された。
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] Adrenergic β receptor activation in the basolateral amygdala, which is intracellular Zn2+-dependent, rescues amyloid β1-42-induced attenuation of dentate gyrus LTP2018
Author(s)
Haruna Tamano, Mitsuyasu Kubota, Yuki Fujise, Ryota Shimaya, Ryusei Itoh, Miki Suzuki, Paul A. Adlard, Ashley I. Bush, Atsushi Takeda
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Journal Title
Neurochem. Int.
Volume: 120
Pages: 43-48
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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