The role of ATBF1 in APP metabolism and A beta production

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500402
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: Nagoya City University
• Principal Investigator: JUNG Cha-Gyun 名古屋市立大学, 医学(系)研究科(研究院), 准教授 (00464579)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アルツハイマー病 / ATBF1 / APP代謝 / Aβ産生

Outline of Final Research Achievements

ATBF1 levels are increased in the cytoplasm of hippocampal neurons in Alzheimer’s disease (AD) brains compared with non-AD brains. Furthermore, cotransfection of human embryonic kidney (HEK293T) and human neuroblastoma (SH-SY5Y) cells with ATBF1 and APP695 increased steady-state levels of APP via the binding of ATBF1 to the APP cytoplasmic domain (amino acids 681-690 domain), resulting in increased Aβ production and cellular and soluble APP (sAPP) levels without affecting the activity or levels of APP processing enzymes (α-, β- or γ-secretase). Conversely, knockdown of endogenous ATBF1 reduced levels of cellular APP, sAPP and Aβ in HEK293 cells overexpressing human APP695. Our findings provide insight into the dynamics of APP processing and Aβ production, and suggest that ATBF1 is a novel APP binding protein that may be a suitable therapeutic target for AD.

Free Research Field

アルツハイマー病、神経科学