2013 Fiscal Year Final Research Report
Identification of receptors for phosphacan which inhibit axonal regeneration
| Project/Area Number |
24890084
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nagoya University |
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Principal Investigator |
SAKAMOTO Kazuma 名古屋大学, 高等研究院(医), 特任助教 (60612801)
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| Project Period (FY) |
2012-08-31 – 2014-03-31
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| Keywords | プロテオグリカン / コンドロイチン硫酸 / ケラタン硫酸 / 神経軸索 / 再生 |
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| Research Abstract |
Highly purified recombinant phosphacan was purepared using anion exchange and gel filtration chromatography. Increasing gradient of recombinant phosphacan induced dystrophic endball, a morphological marker for regeneration stopping axons, to cultured dorsal root ganglion neurons. Using electron microscope and immunocytochemistry, autophagosomes were found in dystrophic endball, suggesting that autophagy is an essential cellular event for formation of dystrophic endball.
Surface plasmon resonance assay revealed that phosphacan strongly bound to PTPsigma and LAR which are known as receptors for chondroitin sulfate. Surprisingly, interaction between phosphacan and PTPsigma or LAR was two-phase manner, and not only chondroitin sulfate but also keratan sulfate were involved in interaction. Free keratan sulfate sugar also bound to PTPsigma and LAR.
PTPzeta, another member of receptors tyrosine phosphatase, was also identified to be involved in inhibition of axonal regeneration.
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[Journal Article] Ablation of keratan sulfate accelerates early phase pathogenesis of ALS2013
Author(s)
Hirano K, Ohgomori T, Kobayashi K, Tanaka F, Matsumoto T, Natori T, Matsuyama Y, Uchimura K, Sakamoto K, Takeuchi H, Hirakawa A, Suzumura A, Sobue G, Ishiguro N, Imagama S, Kadomatsu K
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Journal Title
DOI
Peer Reviewed
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[Journal Article] Minocycline selectively inhibits M1 polarization of microglia2013
Author(s)
Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K, Sakamoto K, Hirakawa A, Takeuchi H, Suzumura A, Ishiguro N, Kadomatsu K
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Journal Title
Cell Death Dis.
Volume: 4
DOI
Peer Reviewed
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