Search for antioxidant compounds with anti-necroptosis effects and investigation of novel treatments for cerebrovascular disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16531
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Josai University
• Principal Investigator: Xuan Meiyan 城西大学, 薬学部, 助教 (50711751)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 抗ネクロトーシス / 抗酸化 / 酸化ストレス / 脳保護効果 / フェルラ酸誘導体

Outline of Final Research Achievements

In cerebral infarction, cell death in the infarct core was believed to be uncontrollable, and treatment had been abandoned. However, in recent years, the existence of "necroptosis" was discovered as a controllable necrotic-like cell death. It has been suggested that inhibition of necroptosis may expand the treatment field for cerebral infarction. In this study, the aim was to search for a compound that has both antioxidant and anti-necroptosis effects as a treatment for cerebral infarction, which is closely related to oxidative stress. The applicant found a candidate compound, FAD041, through screening. FAD041 showed a strong cytoprotective effect against oxidative stress injury, and it was suggested that the antioxidant and anti-necroptosis effects of FAD041 may contribute to the mechanism of action

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は、抗酸化作用とネクロトーシス抑制作用の両方を兼ね備えた化合物を探索することにより、これまで制御不能なネクローシス様細胞死の領域である虚血中心部の障害を含めて、効率よく虚血性細胞死を抑制し、新しい虚血性脳血管障害の治療薬の開発を目指すことにある。ネクトローシスの発見以来、虚血性疾患以外の神経変性疾患、悪性腫瘍、ウイルス感染や免疫性疾患などの組織障害にもこの細胞死が関与することが明らかになっている。また、これらの疾患には、酸化ストレスが大きく関与することから、本研究は、虚血性脳血管疾患のみならず、新しい細胞死が関与する多くの疾患の治療薬の創出にも有意義な情報提供ができると考えている。