Identification and functional analysis of endogenous factors modulating a cutout of Abeta from APP

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293019
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagasaki University
• Principal Investigator: IWATA Nobuhisa 長崎大学, 医歯学総合研究科(薬学系), 教授 (70246213)
• Co-Investigator(Kenkyū-buntansha): Asai Masashi 長崎大学, 医歯薬学総合研究科(薬学系), 助教 (90383223)
• Project Period (FY): 2013-04-01 – 2016-03-31
• 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 / プロテオリシス / 活性調節

Outline of Final Research Achievements

The cause of Alzheimer’s disease is extracellular deposition of amyloid β-peptide (Aβ). Most of Aβ are produced as Aβ40, but Aβ42, which is produced rather in lesser amounts, plays a central role in AD pathogenesis due to its higher aggregation propensity. We previously found that a ratio of Aβ42/Aβ40 production was altered in a differentiation day-dependent manner when we differentiated human iPS cells to neuronal cells, suggesting that gene expression of any factors modulating γ-secretase, which is involved in γ-cleavage of APP-CTFβ, in the cells may be changed during this period. We analyzed changes in gene expression patterns and selected some genes as candidate genes of γ-secretase-modulating factors. We analyzed a ratio of Aβ42/Aβ40 production in cultured medium from cells overexpressing candidate genes. We successfully identified MYT1L and VAT1L as new γ-secretase-modulating factors.

Free Research Field

神経薬理学