Analysis of progranulin as novel therapeutic target against ischemic stroke

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430066
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Niigata University
• Principal Investigator: SHIMOHATA Takayoshi 新潟大学, 脳研究所, 准教授 (60361911)
• Co-Investigator(Renkei-kenkyūsha): KANAZAWA Masato 新潟大学, 医歯学総合病院, 助教 (80645101)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 脳虚血 / プログラニュリン / 神経細胞保護 / 血管保護 / 抗炎症

Outline of Final Research Achievements

We observed that progranulin (PGRN) could protect against acute focal cerebral ischemia by variety of mechanisms, which we call "brain protection", including neuroprotection in part by inhibition of cytoplasmic redistribution of TDP-43 using PGRN knock-out mice, suppression of neuroinflammation via anti-inflammatory interleukin-10 in microglia, and attenuation of blood-brain barrier disruption via vascular endothelial growth factor. We also demonstrated the therapeutic potential of PGRN against acute focal cerebral ischemia using a rat autologous thromboembolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant PGRN significantly reduced volumes of cerebral infarct and edema, suppressed hemorrhagic transformation, and improved motor outcome. PGRN may be a novel therapeutic target that provides brain protection such as vascular protection, anti-neuroinflammation, and neuroprotection.

Free Research Field

神経内科