A construction of new biosensor technology enabling highly sensitive detection of alpha-synuclein fibril originated from Parkinson's disease patient

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K22964
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Kyoto Institute of Technology
• Principal Investigator: Noda Minoru 京都工芸繊維大学, 電気電子工学系, 教授 (20294168)
• Co-Investigator(Kenkyū-buntansha): 山門 穂高 京都大学, 医学研究科, 特定准教授 (10378771) ; 島内 寿徳 岡山大学, 環境生命科学研究科, 准教授 (10335383) ; 寒川 雅之 新潟大学, 自然科学系, 准教授 (70403128)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: パーキンソン病 / αシヌクレイン / リポソーム / 脂質膜 / カンチレバーセンサ / フィブリル / モノマー / 糖脂質

Outline of Final Research Achievements

In this research, the detectivity of aggregated alpha-Syunuclein (aSyn) as a causative agent of Parkinson Disease (PD) was markedly improved by newly developed approaches and techniques. Starting from the aspects of phospholipid membrane, especially, 1) Confirmation on high-sensitivity for the aggregated aSyn down to 10 pg/ml by combination of the interaction with the phospholipid membrane and the self-templating phenomena of aSyn. Improved sensitivities; 2) by concentrating mechanical stress on piezoresistance part of cantilever sensor itself (increased by about an order), 3) by optimizing the salt concentration of target solution (increased by 5 times). Finally, 4) by using the developed biosensor technologies, the serums of PD patients were effectively discriminated from those from non-patients.

Free Research Field

センサ工学

Academic Significance and Societal Importance of the Research Achievements

従来行われるチオフラビンT蛍光色素によるアミロイド線維の染色検出とは異なり、異常凝集性タンパク質のモノマーからオリゴマー、そして線維化に至る線維伸長現象を、モデル細胞膜である脂質膜リポソーム固定化カンチレバーセンサで検出する技術を開発した。現時点で髄液以外に、血清中評価でもパーキンソン病患者、非患者の識別ができる可能性が高く、さらなる本技術レベル向上により臨床応用できればその社会的意義は大きい。