Identification and functional analysis of gamma-secretase-modulating factors

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659034
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• 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): 2012-04-01 – 2015-03-31
• Keywords: アルツハイマー病 / アミロイドβペプチド / γセクレターゼ / プレセニリン / 活性調節

Outline of Final Research Achievements

We previously found that a production ratio of Aβ42/Aβ40 was decreases in a differentiation day-dependent manner when we differentiated human iPS cells to neuronal cells, suggesting that a γ-secretase-modulating factor may be expressed in the cells, because gene expression of any component of the γ-secretase complex was not changed. So, we analyzed a neuronal differentiation day-dependent gene expression profile and selected some genes as a tentative candidate gene of γ-secretase-modulating factor. We cloned the tentative candidate genes, transfected them into neuronal cells, and measured a production ratio of Aβ42/Aβ40 in cultured medium. To date, we identified one of zinc transporter as γ-secretase-modulating factor. Now, we are planning to confirm this function of the zinc transporter using some different experimental paradigms.

Free Research Field

神経薬理学