Identification and functional analysis of brain catechin-binding proteins using aliphatic catechin derivatives

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K14971
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Nagasaki University
• Principal Investigator: IWATA Nobuhisa 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70246213)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: アルツハイマー病 / アミロイドβペプチド / ネプリライシン / αセクレターゼ / βセクレターゼ / カテキン / 結合タンパク質

Outline of Final Research Achievements

I previously found that aliphatic catechin derivatives introduced an alkyl group not only upregulated major Aβ-degrading enzyme neprilysin and α-secretase that cleaves amyloid precursor protein not to generate Aβ, but also downregulated β-secretase via gene expression. In this study, to understand catechin-mediated regulatory mechanism of these gene expressions, I screened catechin-binding proteins for membrane or cytosolic proteins derived from neuronal cells or mouse brains using catechin-coupled magnetic beads and LC/MSMS method, and identified two candidate proteins; one is a secretory vesicle-related protein, and the other is gene expression-related protein. When the neuronal cells overexpressing the candidate protein A or B were treated with aliphatic catechin derivatives, neprilysin activity was more strongly increased than that in mock cells treated with aliphatic catechins, as well β-secrease activity was more prominently suppressed in cells overexpressing the protein A.

Free Research Field

神経薬理学