Development of therapeutic agents for neuropsychiatric disorders targeting the stress-sensitive transcription factor NPAS4

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K08306
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Nagoya City University (2018-2021); Nagoya University (2017)
• Principal Investigator: HIBI YOKO 名古屋市立大学, 大学院医学研究科, 教授 (70295616)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: Npas4 / ストレス / 神経分化

Outline of Final Research Achievements

Since dysfunction of suppressive GABAergic nerves due to decreased expression of NPAS4 may cause nerve excitement / suppression imbalance, we investigated the association with seizures. Npas4-knockout mice were shown to have a lower threshold for convulsions. It was suggested that as the mechanism, Npas4 transcripts Homer1a and gives feedback to suppress nerve excitement. Regarding the search for compounds that induce Npas4 promoter activity, we found several compounds that increase Npas4 promoter activity in humans and mice from commercially available active compound libraries.

Free Research Field

神経薬理学

Academic Significance and Societal Importance of the Research Achievements

神経分化関連転写因子Npas4はストレス負荷により発現が低下することが見いだされており、Npas4の発現低下が神経の興奮/抑制バランスを崩すことによっててんかんなどの疾病の要因となる可能性が示された。また、このNpas4発現を誘導する化合物の探索によって、神経疾患や神経損傷の治療薬の開発の可能性にもつながる。