Revealing oxidative stress in neurodegenerative brain by hydroxyl-radical-focused imaging and proteomics

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K14752
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 37030:Chemical biology-related
• Research Institution: Kyoto University
• Principal Investigator: ZHU Hao 京都大学, 工学研究科, 助教 (90874545)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: reactive oxygen species / hydroxyl radical / conditional proteomics

Outline of Final Research Achievements

Hydroxyl radical is one member of reactive oxygen species (ROS) that regulates diverse biological and pathological processes in living systems. Due to its high reactivity, hydroxyl radical non-selectively modifies biomolecules which is the onset of many human diseases. This research is developing a new method to decipher hydroxyl radical homeostasis in living systems by hydroxyl-radical-responsive protein labeling, which can unravel the localization and surrounding/associated proteins of hydroxyl radical via fluorescence imaging and proteomics. Chemical probes that can be selectively activated by hydroxyl radical for efficient protein labeling have been identified. Preliminary results have demonstrated that such probe enables hydroxyl-radical-responsive protein labeling in response to endogenously produced hydroxyl radicals in macrophages during immune response. Such progress confirmed the feasibility of the proposed concept of hydroxyl radical conditional protein labeling.

Free Research Field

chemical biology

Academic Significance and Societal Importance of the Research Achievements

本研究は、生体内のヒドロキシルラジカルの網羅的な分析を目指し、蛍光イメージングおよびプロテオミクス用のヒドロキシルラジカル応答性タンパク質標識試薬の最初の例を開発します。これは、細胞のヒドロキシルラジカルの分子メカニズムを解明するのに役立つだけでなく、神経変性疾患などの関連疾患の治療薬標的を発見するための手がかりを提供する可能性があります。