The Elucidation of the mechanism of amyloid deposition by combining proteome and lipidome

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: Nippon Medical School
• Principal Investigator: Yukako Shintani-Domoto (新谷裕加子) 日本医科大学, 医学部, 准教授 (30596961)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: アミロイド / プロテオーム / 心血管病理

Outline of Final Research Achievements

Amyloidosis is a disease in which amyloid precursor protein (APP) are deposited in the extracellular matrix and cause organ damage. Currently 42 different APPs have been reported. In the recent years, therapies for some subtypes of amyloidosis have been established but it remains unclear how APP peptides are truncated in vivo during the process of deposition as amyloid. We investigated the distribution of Serum Amyloid A (SAA) and transthyretin (TTR) derived tryptic peptides using Imaging mass spectrometry (MS) and liquid chromatography MS. We showed that the N-terminal SAA2-15 plays a critical role in the formation of SAA fibrils.

Free Research Field

アミロイドーシス

Academic Significance and Societal Importance of the Research Achievements

申請者らは、診断のための病理検査に伴って得られるヒトのホルマリン固定パラフィン包埋（FFPE）検体を用いて、複数の質量分析法を行い、トリプシン消化ペプチド鎖の組織内分布を示すことでアミロイド線維形成と内因性プロテアーゼに関する考察を報告した。
FFPE検体は非侵襲的な方法で得られ、また、各施設において長期保存されているため、希少例が多く含まれている。したがって、FFPE検体を用いて、疾患病態の解明に取り組む試みはアミロイドーシスに限らず他の多くの疾患に応用可能であり、病理検体を用いる全ての研究者にとって有益な研究となり得る。