| Project/Area Number |
20K16468
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 51010:Basic brain sciences-related
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| Research Institution | Juntendo University |
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Principal Investigator |
Cossu Davide 順天堂大学, 健康総合科学先端研究機構, 准教授 (90867326)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | mitophagy / EAE / neuroinflammation / astrocytes / microglia / Parkin / Pink1 / BCG / neuorinflammation / peripheral immunitty / Pink / Parkinson's disease / multiple sclerosis / mitochondria |
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| Outline of Research at the Start |
Neuroinflammation, is reported to have a dual impact on astrocytes activation. At the same time, non-cell autonomous neuronal death might be a mainstream of the inflammation related neurodegenerative process. EAE is a suitable model to study several aspects of CNS inflammation including astrocytes inflammatory signaling. Parkin-knock-out mice exhibit astrocytes abnormalities.
For this reason, the combination of these two-animal models allows us to study the role of astrocytes onto non-cell autonomous neuronal death from a new point of view that has never been carried out until now.
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| Outline of Final Research Achievements |
Our recent research has shown that Parkin, an E3 ubiquitin ligase, modulates peripheral immune cells-mediated immunity during experimental autoimmune encephalomyelitis (EAE). Furthermore, we demonstrated that PTEN-induced putative kinase 1 (PINK1) protein, which acts upstream of Parkin in a common mitochondrial quality control pathway, plays an age-related role in modulating the peripheral inflammatory response during EAE, potentially contributing to the pathogenesis of neuroinflammatory and other associated conditions.
Furthermore, we demonstrated the efficacy of BCG Tokyo-172 vaccine in suppressing actively induced and spontaneous EAE models. Age-related neurorotection was associated with reduced proliferation of splenic T-cells, an elevated frequency of interleukin-10 secreting CD8+ T cells in the spleen and a polarization of microglia and astrocytes towards an anti-inflammatory phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
We demonstrated that mutations in the genes related to mitochondria might contribute to the CNS inflammation, affecting peripheral and glia-dependent immune responses.
Our results also provided new insights into the neuroprotective mechanisms of BCG vaccine, useful for the development of therapies
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