Study for the best matrix environment for neurogenesis in the aged subventricular zone

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07535
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Juntendo University
• Principal Investigator: Arikawa-Hirasawa Eri 順天堂大学, 医学(系)研究科(研究院), 教授 (50245718)
• Co-Investigator(Kenkyū-buntansha): 桝 和子 筑波大学, 医学医療系, 講師 (50344883)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 成体神経新生 / 脱硫酸化酵素 / ヘパラン硫酸プロテオグリカン / 糖鎖修飾 / 細胞外マトリックス

Outline of Final Research Achievements

The purpose of this study is to show a sugar chain modification that rescues the attenuation of neurogenesis signals due to aging, and to explore new therapeutic methods that complement cell and gene therapy. We have so far verified that the expression pattern and sugar chain modification of heparan sulfate proteoglycan (HSPG) are changed in mouse aging SVZ, and the fate control of stem cells is changed. We reported a decrease in proteoglycan groups and an increase in extracellular sulfatase Sulf1 and 2 using them as substrates. Sulf1 / 2, which modifies the 6O-sulfatio of the HS chain to desulfurize extracellularly, regulates the binding of heparin-affinity factors such as GDNF, HGF, and FGF to HSPG extracellularly, and cleverly signals the signals of these factors. However, the details of individual life events are still unknown. Therefore, in this study, we use Sulf1 / 2 DKO to clarify the direct involvement of Sulfur and neurogenesis and the related molecular mechanism.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

成体神経新生の存在が示され、神経変性疾患治療の選択肢が拡がることに期待が高まった。しかし、加齢に伴い神経新生領域の一つである脳室下帯（SVZ）では神経新生が減弱することが知られ、ニューロンの存在環境は極めて厳しいとされる。本研究により、老化による神経新生シグナルの減弱をレスキューする糖鎖修飾/細胞外環境（ベストマトリクス環境）が示されれば、細胞、遺伝子治療を補完する新規治療方法を探ることが可能になる。超高齢社会における神経再生の一助となると期待される。