Functional analysis of Smek2 which regulates metabolisms of three major nutrients

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K14806
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 38050:Food sciences-related
• Research Institution: Kyushu University
• Principal Investigator: Yasutake Tanaka 九州大学, 農学研究院, 助教 (90809435)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Smek2 / アミロイドβ / アルツハイマー型認知症

Outline of Final Research Achievements

The aim of this study is to analyze the function of the Smek2 gene, which was identified as one of the causative genes for diet-induced hypercholestereoemia in exogenous hypercholesterolemic (ExHC) rat. To achieve this aim, we tried to creat Smek2 knockout rats using the CRISPER/Cas9 system and to establish an in vitro Smek2 overexpression system. While we did not achieve to create Smek2 knockout rats due to technical problems, we succeeded in constructing a vector for an overexpression system to conduct an overexpression experiment with human neuroblast cells. As a result, overexpression of Smek2 decreased the amount of amyloid β contained in the cell culture supernatant. This suggested that Smek2 may control suppressively amyloid-β production in the brain. This result may bring new developments to Alzheimer's disease research.

Free Research Field

栄養学

Academic Significance and Societal Importance of the Research Achievements

Smek2に欠損変異のあるExHCラットの脳ではアミロイドβの蓄積が見られたことから、Smek2はアルツハイマー型認知症の発症・進展においても重要な意味を持つ遺伝子であると考えてきた。今回、ヒト神経芽細胞腫 SH-SY5Y 細胞における過発現実験において、Smek2過発現によってアミロイドβ量が減少したことから、そのことが裏付けられる形となった。これまでアルツハイマー型認知症研究の対象となる遺伝子はアミロイドβそのものあるいはその切断酵素（βセクレターゼ）であったため、本成果はアルツハイマー型認知症研究に新たな展開をもたらす可能性がある。