Pathological and cytological sesearch of neurodegenerative diseases and earch for therapeutic drug candidates based on OPTN dysfunction
| Project/Area Number |
16K18383
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Kyoto University |
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Principal Investigator |
ayaki takashi 京都大学, 医学研究科, 特定病院助教 (60749555)
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | optineurin / NF-кB / multiple proteinopathy / 神経細胞死 / NLRP3インフラマソーム / ミクログリア / 顆粒空砲変性 / 直鎖型ユビキチン / OPTN / NF kappa B / 顆粒空胞変性 / インフラマソーム / 直鎖状ユビキチン鎖 / 活性型カスパーゼ3 / 神経炎症 / 選択的オートファジー / 筋萎縮性側索硬化症 / NFκB / 神経変性疾患 |
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| Outline of Final Research Achievements |
Through the elucidation of OPTN-mediated autophagy and neuroinflammation signals, we examined the pathogenesis of ALS, Alzheimer's disease and multiple system atrophy. The role of autophagy in ALS has been reported by the presence of multiple protein aggregates in ALS. As for neuroinflammatory signals, we confirmed and reported that phosphorylated p65 (an active form of the NF kappa B signal molecule), is aggregated in the hippocampus of Alzheimer's disease and ALS-OPTN. In addition, we examined NLRP3 inflammasome-related proteins in multiple system atrophy microglia in autopsied brains and reported the relationship between α-synuclein and NLRP3 inflammasome-related protein-positive microglia.
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| Academic Significance and Societal Importance of the Research Achievements |
OPTNに関連したたんぱく質の異常の探求を通じて、これまで、不明であった変性疾患におけるオートファージー、神経炎症シグナルの異常がALS やアルツハイマー病や多系統萎縮症において示された。シグナル異常が変性疾患の治療対象になる可能性が示唆された。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Multiple proteinopathies in familial ALS cases with optineurin mutation.2017
Author(s)
Ayaki T, Ito H, Komure O, Kamada M, Nakamura M, Wate R, Kusaka H, Yamaguchi Y, Li F, Kawakami H, Urushitani M, Takahashi R
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Journal Title
J Neuropathol Exp Neurol
Volume: 77
Issue: 2
Pages: 128-138
DOI
Related Report
Peer Reviewed
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[Journal Article] Linear ubiquitination is involved in the pathogenesis of optineurin-associated amyotrophic lateral sclerosis.2016
Author(s)
Nakazawa S, Oikawa D, Ishii R, Ayaki T, Takahashi H, Takeda H, Ishitani R, Kamei K, Takeyoshi I, Kawakami H, Iwai K, Hatada I, Sawasaki T, Ito H, Nureki O, and Tokunaga F.
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Journal Title
Nat. Commun.
Volume: 7
Issue: 1
Pages: 12547-12547
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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