Development of preventive and therapeutic treatments based on the pathogenesis of the transmission of amyloidosis

2016 Fiscal Year Final Research Report

• Project/Area Number: 26293084
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Shinshu University
• Principal Investigator: HIGUCHI Keiichi 信州大学, 学術研究院医学系, 教授 (20173156)
• Co-Investigator(Kenkyū-buntansha): 澤下 仁子 信州大学, 学術研究院医学系, 助教 (40359732) ; 森 政之 信州大学, 学術研究院医学系, 准教授 (60273190) ; 亀谷 富由樹 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 主席研究員 (70186013) ; 矢崎 正英 信州大学, 学術研究院医学系, 准教授 (70372513)
• Co-Investigator(Renkei-kenkyūsha): NAKAMURA Soichiro 信州大学, 役員等, 理事 (00105305)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 実験病理学 / アミロイドーシス / 蛋白質 / 疾患モデル動物 / 伝播 / ApoA-II / トランスサイレチン / 治療

Outline of Final Research Achievements

We investigated mouse AApoAII amyloidosis and in vitro fibril formation to understand the pathogenesis of the transmission of amyloidosis and develop new therapeutic treatments. We revealed that 1) Treatment with the fibril-formation-inhibitory peptide which blocks the active ends of amyloid fibrils for seeding reaction prevented amyloid deposition in amyloidosis induced mice. 2) Amyloid deposition could be induced by the injection of white blood cells (lymphocyte and monocyte) or red blood cells isolated from amyloid-laden mice. 3) Caloric restriction (60% CR) improved ApoA-II metabolism, inflammation and mitochondria function, and suppressed amyloid deposition. 4) Wild and variant TTR amyloid proteins were identified in the small area cut out from tissue sections of patients with accelerated amyloid deposition after domino liver transplantation using laser micro dissection and mass spectrometry analysis.

Free Research Field

実験病理学