Novel strategy for the development of therapeutics against autoimmune disease of the central nervous system, utilizing the crosstalk of cells forming blood-brain barrier.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04197
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Yamaguchi University
• Principal Investigator: KANDA Takashi 山口大学, 大学院医学系研究科, 教授 (40204797)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 血液脳関門 / ペリサイト / 内皮細胞 / 低分子化合物 / アストロサイト / 脂質メディエーター

Outline of Final Research Achievements

Twenty selective lipid mediator receptor agonists, screened to be permeable through blood-brain barrier (BBB), were analyzed. After adding in the culture media for BBB multi-culture model composed of human endothelial cell, pericyte and astrocyte, upregulation of BDNF in aliquot was observed in two compounds, EP4 agonist and S1P5 agonist. Since these two compounds also increase the production of BDNF in astrocyte monoculture, we concluded that they may go through endothelial cell/pericyte layer, and affect astrocyte directly to enhance the production of BDNF.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

今回同定した2種類の脂溶性化合物は、中枢神経内での神経栄養因子の産生を促すことによって中枢神経実質の内部環境を神経再生の方向に改変する神経変性疾患治療薬のリード化合物としての可能性があるだけでなく、BBB調節のための栄養因子の分泌を人為的に制御できる可能性があり、高分子治療薬を中枢神経内に流入させる際の補助治療薬となりうると考えられた。