Purinergic regulation of dying cell phagocytosis and production of inflammatory and protective factors by microglia
Project/Area Number |
15K08234
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
General pharmacology
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Research Institution | Hiroshima University |
Principal Investigator |
Hide Izumi 広島大学, 医歯薬保建学研究科(医), 助教 (20253073)
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Co-Investigator(Kenkyū-buntansha) |
酒井 規雄 広島大学, 医歯薬保健学研究科(医), 教授 (70263407)
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Research Collaborator |
TANAKA SHIGERU
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | ミクログリア / 貪食 / トル様受容体4 / P2Y受容体 / ATP / 神経保護 / トル様受容体 / ATP受容体 / P2Y2受容体 / 死細胞貪食 / TAM受容体 |
Outline of Final Research Achievements |
Microglia, resident macrophages of the CNS, play important roles in neuroprotection and neurodegeneration. Lipopolysaccharide (LPS) stimulation caused death of microglia, whereas a portion of microglia survived for a long time. The long-lived microglia were highly phagocytic and exerted protective function. Microglial P2Y2 receptor was involved in phagocytosis of dying cells or neurons. Expression of inflammatory mediators, TNF-alpha or iNOS, was also regulated via P2Y2 receptor. Production of protective factor, activin A, and anti-inflammatory cytokine IL-10 was mediated via P2Y13 receptor, suggesting a novel role of P2Y13 receptor in microglial neuroprotection.
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Academic Significance and Societal Importance of the Research Achievements |
アルツハイマー病やパーキンソン病などの神経変性疾患の病態にはミクログリアの活性化と慢性炎症が関与する。また、自閉症などの神経疾患にも炎症とミクログリアの過剰な貪食の関与が示唆されている。本来脳を守るミクログリアが神経傷害を引き起こしてしまう機序として、本研究で示した異なる機能をもつサブセットの存在が考えられる。また、貪食にも炎症因子の産生にも関与するP2Y2受容体は自閉症治療薬スラミンの標的でもあり、スラミンは過剰な貪食と炎症反応を抑制することにより病態を改善する可能性がある。さらにP2Y13受容体の保護的役割も明らかとなり、今後、難治性神経疾患の新しい治療法の開発に繋がることが期待される。
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Report
(5 results)
Research Products
(61 results)
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[Journal Article] The Role of Cysteine String Protein Alpha (CSPα) Phosphorylation at Serine 10, and 34, by Protein Kinase Cγ for Presynaptic Maintenance.2018
Author(s)
Shirafuji T, Ueyama T, Adachi N, Yoshino KI, Sotomaru Y, Uwada J, Kaneoka A, Ueda T, Tanaka S, Hide I, Saito N, Sakai N
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Journal Title
J. Neurosci.
Volume: 38
Issue: 2
Pages: 278-290
DOI
Related Report
Peer Reviewed
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[Journal Article] Validation of Anti-CSPα, SNAP25, Tyrosine Hydroxylase, Ubiquitin, Cleaved Caspase 3, and pSer PKC Motif Antibodies for Utilization in Western Blotting2017
Author(s)
Shirafuji T, Ueyama T, Tanaka S, Hide I, Saito N and Sakai N
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Journal Title
ACTA HISTOCHEMICA ET CYTOCHEMICA
Volume: 50
Issue: 6
Pages: 177-180
DOI
NAID
ISSN
0044-5991, 1347-5800
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Toll-like receptor 4-activated neuroprotective microglia subpopulation survives via granulocyte macrophage colony-stimulating factor and JAK2/STAT5 signaling2016
Author(s)
Kamigaki, M., Hide, I., Yanase, Y., Shiraki, H., Harada, K., Tanaka, Y., Seki, T., Shirafuji, T., Tanaka, S., Hide, M., and Sakai. N.
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Journal Title
Neurochem. Int.
Volume: 93
Pages: 82-94
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] The Development of Screening Methods to Identify Drugs to Limit ER Stress Using Wild-type and Mutant Serotonin Transporter2016
Author(s)
Katarao, K., Murakawa, S., Asano, M., Usuki, N., Yamamoto, H., Shirafuji, T., Tanaka, S., Hide, I. and Sakai, N.
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Journal Title
ACTA HISTOCHEMICA ET CYTOCHEMICA
Volume: 49
Issue: 6
Pages: 197-206
DOI
NAID
ISSN
0044-5991, 1347-5800
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] The role of Cysteine string protein alpha (CSPa) phosphorylation at Ser10 and Ser34 by PKCg for the presynaptic maintenance2017
Author(s)
Shirafuji, T., Ueyama, T., Adachi, N., Yoshino, K., Tanaka, S., Hide, I., Saito, N., Sakai, N.
Organizer
第23回世界神経学会議/第58回日本神経学会学術大会
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