| Project/Area Number |
17K07089
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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 |
Nerve anatomy/Neuropathology
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| Research Institution | Hirosaki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
三木 康生 弘前大学, 医学研究科, 助教 (30709142)
若林 孝一 弘前大学, 医学研究科, 教授 (50240768)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 神経難病 / 認知症 / パーキンソン病 / レビー小体型認知症 / 多系統萎縮症 / シヌクレイン / 検出方法 / シヌクレイノパチー / リン酸化 / 脳神経疾患 / 神経科学 / 老化 / 病理学 / 脳・神経 |
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| Outline of Final Research Achievements |
Neurodegenerative diseases are characterized by the aggregation of specific molecules, especially alpha-synuclein (Syn), which is aggregated in the brains of patients with Parkinson’s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA), which are called synucleinopathies.
We revealed that NUB1 coexists with abnormal Syn in LB disease patients and Tg mice expressing Syn, raising the possibility that NUB1 highly contributes to pathogenesis of synucleinopathies.
In this study, we found that post-modified NUB1 is different from native NUB1 especially, phosphorylation of NUB1 at S46 (P-NUB46) exhibited the greatest impact on the degradation of aggregates and cell-viability. Using our specific antibody against P-NUB46, we found that NUB1 is indeed phosphorylated at S46 in the brain, and P-NUB46 levels are significantly higher in DLB brains than in control brains. These findings suggest that P-NUB46 plays a important role in the pathogenesis of synucleinopathies.
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| Academic Significance and Societal Importance of the Research Achievements |
パーキンソン病（PD）やレビー小体型認知症（DLB）を早期に診断できれば、早期から治療を開始することができる。しかし上述したように、健常者の脳にある正常なSynと患者脳内の異常Synを区別できないため検出法の精度が低く、実用化には至っていない。2017年～2019年に得た知見は、これまでに培ってきた技術と知識をさらに発展させたものである。早期のPD、DLBの診断を可能にする簡易な検出系を開発する準備が整ったといえる。
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