Development of novel therapeutic strategies for sickle cell disease by activating Nrf2

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461395
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Tohoku University
• Principal Investigator: Suzuki Mikiko 東北大学, 医学系研究科, 講師 (80508309)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 鎌状赤血球症 / Nrf2 / 酸化ストレス

Outline of Final Research Achievements

Sickle cell disease (SCD) is an inherited disease caused by a mutation in globin gene. Hemoglobins containing the mutated globin polymerize in red blood cells (RBC) and deform RBC into a sickle-like shape. The sickle-shaped RBCs are prone to intravascular hemolysis and intermittent blood glow occlusion, which results in ischemia-reperfusion injury generating oxidative stresses. Nrf2 is a transcription factor that induces expression of target genes involved in cellular defense against oxidative stresses. In this study, we found that genetic and pharmacologic activation of Nrf2 ameliorated tissue damages and inflammation in SCD model mice, indicating that Nrf2 activation relieves symptoms of SCD. Based on these results, we propose that Nrf2 is a therapeutic target for the treatment of SCD.

Free Research Field

医化学