Identifying the first pathological change for the new therapeutic target in ALS
| Project/Area Number |
15K08368
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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 |
Human pathology
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| Research Institution | Toho University |
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Principal Investigator |
KANO Osamu 東邦大学, 医学部, 教授 (20459762)
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| Co-Investigator(Kenkyū-buntansha) |
石川 由起雄 東邦大学, 医学部, 客員教授 (30276894)
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| Research Collaborator |
HOSHI Hideo
URITA Yoshihisa
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥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 / 脱神経 / 炎症 / dying back |
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| Outline of Final Research Achievements |
Neuroinflammation is a prominent pathologic feature in the spinal cord in Amyotrophic lateral sclerosis (ALS). The presence of inflammation surrounding the degenerating peripheral nerve fibers is an early event that occurs prior to the onset of motor weakness. However, we do not know whether the peripheral nerve inflammatory response initiates, or in response to, the neurodegenerative process. We evaluated denervation and accompanying inflammatory responses longitudinally in the cervical spinal cord-phrenic nerve-diaphragm motor units and lumbar spinal cord-sciatic nerve-gastrocnemius units of mSOD1Tg mice. Our result showed that denervation occurred prior to inflammation in both units. Hence, peripheral inflammation is not the cause of denervation, but a response to the neurodegeneration. We have to consider the peripheral as a therapeutic target in addition to spinal cord.
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| Academic Significance and Societal Importance of the Research Achievements |
ALSの形態学的初発変化が脊髄より末梢神経であり、さらに脱神経が末梢神経の炎症に先行してみられることが示された。これまで、脊髄運動ニューロンの変性に対する治療がメインであったが、経時的な変化を考えると、新たな治療ターゲットとして脱神経や炎症を抑える治療の方がより効果的といえる。今後の創薬分野において、新たな方向性を示すことができた。
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Report
(5 results)
Research Products
(3 results)
