Investigation of reduced expression and activity of an amyloid-degrading enzyme in Down syndrome

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K07070
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Yokohama College of Pharmacy
• Principal Investigator: Asai Masashi 横浜薬科大学, 薬学部, 講師 (90383223)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: アルツハイマー病 / ダウン症 / 21番染色体 / DYRK1A / 阻害剤 / in silico

Outline of Final Research Achievements

To development novel drugs for Alzheimer’s disease, we focused on DYRK1A, which is involved in both APP and tau, and aimed to find compounds that inhibit DYRK1A in silico. Based on the reported structures of compounds that inhibit DYRK1A, the interaction of the compounds with DYRK1A was compared using the integrated computational chemistry system MOE. Based on the general-purpose compound harmine, the compounds possessed in the laboratory were examined. As a result, compounds with higher affinity than harmine were found. Furthermore, compounds with stronger affinity were successfully prepared by adding or exchanging substituents of compounds with high affinity.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、in silicoでのDYRK1Aの阻害剤開発を行い、実験で汎用されている化合物であるharmineよりもDYRK1Aに親和性が高い化合物を見出した。本化合物およびその誘導体のDYRK1Aとの予測される相互作用は非常に強力なものであり、アルツハイマー病の有用な治療薬になる可能性が高い。