The origin of retrograde motor neuron degeneration elicited by activated microglia in pre- or early-symptomatic spinal cord tissues from human patients with amyotrophic lateral sclerosis
| Project/Area Number |
16K09721
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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 |
Neurology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
山崎 亮 九州大学, 医学研究院, 准教授 (10467946)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 筋萎縮性側索硬化症 / 脊髄前側索 / galectin-3 / p22phox / osteopontin / microglia / macrophage / ミクログリア / 活性化ミクログリア / 運動ニューロン変性 / TDP-43 / 遺伝子 / 脳神経疾患 |
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| Outline of Final Research Achievements |
We previously reported that in 70% of ALS spinal cords, massive microglia/macrophages (Mi/Mφ) were observed not only in the corticospinal tract (CST) but also in the anterolateral funiculus outside the CST (ALFoc). Among various neurodegenerative diseases, those Mi/Mφ distributions in ALS spinal cords are extremely unique; however, its significance still remains to be elucidated. To address this issue, we explored various molecules expressed in activated Mi/Mφusing spinal cord specimens from human patients with ALS in the present study. The results revealed that; (1) The number of galectin-3-immunoreactive Mi/Mφ in the ALFoc was positively correlated with that of motor neurons with TDP-43 pathology in ALS spinal cords at terminal stage. (2) Many p22-immunopositive Mi/Mφ were observed in the ventral grey matter with abundant motor neurons in early-symptomatic ALS spinal cords.
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| Academic Significance and Societal Importance of the Research Achievements |
ALS病態において運動ニューロン毒性を発揮する候補分子としてgalectin-3を同定したことは、神経変性疾患全体として見ても画期的な分子標的療法を開発する糸口となり得る。発症早期病巣に豊富に認められたp22は、本疾患として初の早期診断マーカー（血清や脳脊髄液を用いて測定可能と推測される）として利用できる可能性を示す。本研究の知見により、今後ALS患者が発症早期の段階で負担の少ない検査で正しく診断され、根治的な治療を享受する機会が得られれば、学術的にも社会的にも意義のある成果である。
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Report
(4 results)
Research Products
(23 results)
