2015 Fiscal Year Final Research Report
Identification and functional analysis of endogenous factors modulating a cutout of Abeta from APP
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
|