Oral inflammation induces Parkinson disease via production of oxidized synuclein

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07402
• 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: Aichi Gakuin University
• Principal Investigator: Maruyama Wakako 愛知学院大学, 健康科学部, 教授 (20333396)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: パーキンソン病 / 口腔炎症 / 酸化ストレス / ミエロペルオキシダーゼ

Outline of Final Research Achievements

It was suggested that toxic alpha-synuclein (aSyn) oligomer synthesized in the enteric nervous system was transported into the brain to cause neurodegeneration in Parkinson disease (PD). Oral cavity is the most rostral part of gastrointestinal tract but little is known about the role of oral inflammation and oxidative stress in the synthesis of PD causative toxic aSyn. Human saliva obtained from elderly facility residents, and outpatients with PD and control was analyzed. The activity of myeloperoxidase (MPO), the enzyme produced and released from activated neutrophils was found to be a sensitive biomarker for early oral inflammation, and the activity was significantly increased in PD patient compared to the control. The mechanism of the increased MPO activity was studied. It was found that increased MPO activity was not due to the increased protein level, but there exists an intrinsic factor which regulates the enzyme activity.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本課題では、パーキンソン病 (PD)における口腔炎症の役割を明らかとするため研究を行った。口腔炎症を客観的定量的に評価するバイオマーカーは未だ確立していないが、活性化好中球から分泌される酵素であるmyeloperoxidase (MPO)活性が歯周病の早期像である歯肉炎患者の唾液で有意に増加し、病勢の進行と共に低下することを見出した。MPOは早期口腔炎症の生化学的マーカーとして有用である可能性がある。MPOはPD唾液で増加しており、クロロラジカルを生成を介して酸化ストレスによる組織傷害を起こす。MPO活性の制御機構について今後の研究が必要である。