Molecular pathological environments promoting/inhibiting the development of amyloidosis: the synergistic interaction of protein science and animal models

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293094
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Fukui
• Principal Investigator: Naiki Hironobu 福井大学, 医学部, 教授 (10227704)
• Co-Investigator(Kenkyū-buntansha): HIGUCHI Keiichi 信州大学, 学術研究院医学系, 教授 (20173156) ; HASEGAWA Kazuhiro 福井大学, 医学部, 助教 (60324159) ; OZAWA Daisaku 福井大学, テニュアトラック推進本部, 助教 (60554524) ; OOKOSHI Tadakazu 福井大学, 医学部, 助教 (90362037)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アミロイドーシス / アミロイド線維 / β2-ミクログロブリン / 細胞外シャペロン / 血清アミロイド成分 / C反応性蛋白質 / 細胞傷害 / トランスジェニックマウス

Outline of Final Research Achievements

(1) We found that C-reactive protein (CRP) and serum amyloid P component (SAP) may be a member of extracellular chaperones, and the pro- and anti-amyloidogenic activities of SAP are not mutually exclusive, but reflect two sides of the same coin. (2) We found that β2-microglobulin (β2-m) amyloid fibrils endocytosed by the cultured rabbit synovial fibroblasts induce necrosis and apoptosis by disrupting endosomal/lysosomal membranes, proposing a novel mechanism on the cytotoxicity of amyloid fibrils. (3) We histopathologically analyzed the distribution of glycosaminoglycans and proteoglycans in the β2-m amyloid deposits and found the specific distribution patterns of individual molecules. (4) We found that basement membrane components accelerate the initiation of amyloid β-peptide fibril growth in vitro, supporting the essential role of vascular basement membranes in the development of cerebral amyloid angiopathy.

Free Research Field

病理学