Development of new natural resources and discovery of novel medicinal seeds for anti-Alzheimer disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07143
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47050:Environmental and natural pharmaceutical resources-related
• Research Institution: Meiji Pharmaceutical University
• Principal Investigator: Takatori Kaoru (Kaoru Kinoshita) (木下薫) 明治薬科大学, 薬学部, 教授 (40247151)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 新規天然資源 / アルツハイマー病 / アミロイドβ凝集抑制 / BACE1 / サボテン科植物 / キノコ子実体 / 海洋由来真菌 / 発酵

Outline of Final Research Achievements

The mechanism of Alzheimer's disease is the production and aggregation of amyloid-β (Aβ)peptides in the brain. Amyloid-β is produced by the proteolytic cleavage of the amyloid precursor protein by β-secretase (BACE1) and γ-secretase. In this study, we search the compounds which showed BACE-1 inhibitory activity and Aβ aggregation inhibitory activity from newly developed natural resources, cacti, marine-derived fungi and mushrooms. The new natural resources were developed using histone deacetylase (HDAC) inhibitor to activate the biosynthetic genes. Marine-derived fungi were cultured with HDAC inhibitors for the production of new secondary metabolites. The new compounds were produced from newly developed natural resources.
Some new saponins isolated from cacti showed Aβ aggregation inhibitory activity and some compounds isolated from marine-derived fungi and mushrooms showed Aβ aggregation inhibitory activity and BACE1 inhibitory activity.

Free Research Field

天然物化学

Academic Significance and Societal Importance of the Research Achievements

現在，アルツハイマー病に対する根本的な治療薬はなく，症状の進行を抑える対処療法的な治療薬としてアセチルコリンエステラーゼ阻害薬などがあるのみである．従って根本的な治療薬の開発が急がれている．このような背景から，本研究ではアルツハイマー病の原因とされるアミロイドβの産生と凝集を阻害するという根本的治療薬となりうる化合物を天然資源から見いだすことを目的としている，本研究では既存の資源から複数の作用点を有する抗アルツハイマー活性を有する化合物を見いだすことに成功したことから，新たなアルツハイマー病治療薬の開発に繋がる研究である。