Pathophysiologic significance of the receptor binding protein in the central nervous system

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23974
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Yokohama City University
• Principal Investigator: KINGUCHI Sho 横浜市立大学, 附属病院, 助教 (30846986)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: ATRAP / レニンーアンジオテンシン系 / 認知症 / 高血圧 / 糖尿病

Outline of Final Research Achievements

Renin-angiotensin system (RAS) could be associated with cognitive dysfunction. Angiotensin II type 1 receptor (AT1R)-associated protein (ATRAP) may function as an endogenous inhibitor that suppresses AT1R hyperactivation and improve cognitive dysfunction. Recently, cognitive function is easy to decrease in patients with hypertension, or diabetes. The purpose of this study is to investigate expression of RAS components and pathophysiologic significance of ATRAP in central nervous system using hypertension model animal.

Free Research Field

腎臓，高血圧

Academic Significance and Societal Importance of the Research Achievements

中枢神経におけるR-A系の過剰活性化が，認知症の発症・進展に関わる可能性がある．だが，R-A系は生体内の恒常性維持を担う重要な生理的調節系でもある．この恒常的生理機能維持を担うR-A系の生理的情報伝達系活性への遮断を回避し，同受容体系の病的な過剰活性化のみを選択的に抑制することが重要である．研究代表者らは，ATRAPが生理的なAT1受容体情報伝達系活性に影響を与えずに病的な過剰活性化のみを選択的に阻害するという機能上の大きな利点をもつ可能性を報告してきた．本研究はATRAPの認知症改善機能に着目し，その機能上の独自性から従来のR-A系阻害とは異なる観点の重要な成果が得られる可能性が高い．