The study about the mechanism underlying brain iron accumulation in the deficiency of iPLA2 beta.
Project/Area Number |
24591294
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Osaka University |
Principal Investigator |
BECK Goichi 大阪大学, 医学部附属病院, 医員 (20626353)
|
Co-Investigator(Kenkyū-buntansha) |
SUMI Hisae 大阪大学, 医学系研究科, 助教 (30403059)
MOCHIZUKI Hideki 大阪大学, 医学系研究科, 教授 (90230044)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
|
Keywords | NBIA2 / PLA2G6 / DMT1 / 鉄調節蛋白質 / ミトコンドリア / NBIA / IRP / 神経筋疾患 / 神経病理 / カルシウム非依存性フォスフォリパーゼA2β / SH-SY5Y細胞 |
Outline of Final Research Achievements |
Mutations in PLA2G6 (iPLA2 beta) have been proposed to be the cause of neurodegeneration with brain iron accumulation type 2. The present study aimed to clarify the mechanism underlying brain iron accumulation during the deficiency of iPLA2 beta. We demonstrated that marked iron deposition was observed in the brains of PLA2G6-KO mice since the early clinical stages. Divalent metal transporter 1 (DMT1) and iron regulatory proteins (IRPs) were markedly upregulated in the brains of aged PLA2G6-KO mice compared to age-matched wild-type control mice. DMT1 and IRPs were significantly upregulated in PLA2G6-KD cells. Degeneration of the mitochondrial inner membrane and decrease of ATP production were observed in PLA2G6-KD cells. These results suggest that the genetic ablation of iPLA2 beta increased iron uptake in the brain through the activation of IRPs and upregulation of DMT1, which was induced by mitochondrial dysfunction.
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Report
(4 results)
Research Products
(18 results)