Challenges to the hypothesis that the blood-arachnoid barrier efflux transport systems function as central nervus system detoxification system

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22599
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: The University of Tokushima
• Principal Investigator: TACHIKAWA Masanori 徳島大学, 大学院医歯薬学研究部(薬学域), 教授 (00401810)
• Co-Investigator(Kenkyū-buntansha): 斉藤 貴志 名古屋市立大学, 医薬学総合研究院(医学), 教授 (90360552) ; 吉良 潤一 国際医療福祉大学, 福岡薬学部, 教授 (40183305)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: 血液くも膜関門 / 排出輸送

Outline of Final Research Achievements

This study aims to validate our hypothesis that the blood-arachnoid barrier possesses the dynamic clearance system for neurotoxic substances in the cerebrospinal fluid and functions as a central nervus system detoxification system. The present study has proposed that α-synuclein, a pathogenic protein, which is known to be and accumulated in the brain of the Parkinson’s disease, would undergo the LDL receptor-related protein-mediated efflux transport from the cerebrospinal fluid. The study has also established the comprehensive proteomics and the LC-MS/MS-based targeted absolute quantification system for extracellular vesicles, pathogenic proteins, peptides, and metabolites to clarify various efflux transport system at the blood-arachnoid barrier.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

従来、くも膜は脳や脊髄を物理的に保護するための単なる支持被膜であるとの考えが通説であった。これに対し本研究は、「中枢環境を規定し、中枢解毒装置として機能する、動的インターフェースとしての血液くも膜関門輸送系の役割」という新たな概念を構築し、血液くも膜関門の機能破綻と中枢神経病態との関連性解明に迫るものであり、中枢病態の解明や治療法の開発へ突破口を開く潜在性を有している点において、学術的意義だけでなく社会的意義を有する。