Identification and Role of a Novel Blood Tryptophan-Kynurenine Carrier Associated with the Pathophysiology of Depression

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07369
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Kyushu University
• Principal Investigator: Setoyama Daiki 九州大学, 大学病院, 助教 (30550850)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: うつ病 / トリプトファン / キヌレニン / 血中運搬因子 / プロテオミクス

Outline of Final Research Achievements

Tryptophan-kynurenine metabolites are associated with depression and are bound to some unidentified transport proteins in the blood. The aim of this study was to identify the transport proteins and to analyze their association with the pathophysiology of depression. We identified them by gel filtration SDS-PAGE and mass spectrometry of plasma proteins, established a method for quantifying blood levels of the proteins, and evaluated their association with depression. Blood levels of alpha2-macroglobulin (A2M), identified as a tryptophan transport protein, were significantly decreased in the depressed patient group. In addition, proteomic analysis was performed to search for other tryptophan-kynurenine transporters in 300 plasma proteins, and several candidate binding factors were identified.

Free Research Field

生体分子解析学

Academic Significance and Societal Importance of the Research Achievements

本研究は、大うつ病に関連するトリプトファン・キヌレニン代謝物の運搬因子としてα2マクログロブリン(A2M)を同定し、その血中レベルがうつ病患者で有意に低下していることを発見した。さらにプロテオミクス解析により、新たな結合因子候補も多数同定された。これらの結果は、うつ病の生物学的メカニズムの理解へのきっかけを見出し、新たな診断基準や個別化医療の発展に寄与する可能性があります。A2Mの定量法の確立は、診断や治療効果のモニタリングにおいて重要であり、うつ病患者のケアの質向上に繋がると考えられる。