Elucidation of the mechanism of reactive nitrogen species-induced neuronal cell death using small molecules

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K05343
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Azabu University
• Principal Investigator: Kamisuki Shinji 麻布大学, 獣医学部, 准教授 (30553846)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 神経保護物質 / 微生物二次代謝産物 / 活性窒素種

Outline of Final Research Achievements

Reactive nitrogen species-induced neuronal cell death is known to be associated with neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. In the present study, we purified fungal secondary metabolites to construct a chemical library, and screened the chemical library for small molecules that protect from reactive nitrogen species-induced cell death. As a results, we discovered a novel neuroprotective compound, pestalotioquinol A. Pestalotioquinol A did not exhibit cytoprotective effect on reactive oxygen species-induced cell death, which suggested that cytoprotection of pestalotioquinol A is specific for reactive nitrogen species.

Free Research Field

ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病やパーキンソン病などの神経変性疾患は、多くの場合老化と共に発症する難病であり、高齢化社会において深刻な問題となっている。活性窒素種は神経変性疾患だけでなく炎症性疾患などとの関連性も知られており、本研究により見出されたpestalotioquinol Aはこれらの治療薬への応用も期待できる。また、この化合物は活性窒素種特異的な保護作用を示すというユニークな作用をもつことから、今後詳細な作用機序を解析することで、活性窒素種に対する細胞傷害機構・防御機構の解明につながる可能性がある。