Elucidation of molecular basis for the pathogenesis of AA amyloidosis based on the compositional analysis of biomolecules

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08436
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Tanaka Masafumi 神戸薬科大学, 薬学部, 講師 (40411904)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: アミロイドーシス / 血清アミロイドA / 高密度リポタンパク質 / グリコサミノグリカン / ペプチドライゲーション

Outline of Final Research Achievements

Human serum amyloid A (SAA) is a precursor protein of AA amyloidosis. Besides an increase in blood levels of SAA, interactions between SAA and other biological components contribute to the onset of AA amyloidosis. However, the molecular basis that directly links these interactions with the onset of disease has not been fully elucidated. In the present study, we aimed to clarify the influence of glycosaminoglycans and lipid constituents in high-density lipoproteins (HDLs) on the pathogenesis of AA amyloidosis. Our research revealed that the highly sulfated domains in heparan sulfate and the concentration of phosphatidic acid in HDLs affect the onset of AA amyloidosis. In the future, we will continue to evaluate the underlying mechanism of AA amyloidosis at the molecular level by evaluating the cytotoxicity of aggregates formed by SAA.

Free Research Field

生物物理化学