Analysis of the function of Rho-ROCK signal in dementia disease

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09684
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Fujita Health University
• Principal Investigator: Wakita Hideaki 藤田医科大学, 医学部, 教授 (80416172)
• Co-Investigator(Kenkyū-buntansha): 水谷 謙明 藤田医科大学, 共同利用研究推進施設, 講師 (30351068)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 血管性認知症 / アルツハイマー病 / Rho-kinase / 認知症モデル動物 / Rho / LIM-kinase

Outline of Final Research Achievements

In this study, we elucidated the role of Rho-ROCK signal in dementia disease by analyzing the brains of dementia model animals. In vascular dementia model rats, it was revealed that ROCK1, RhoB or LIM-kinase2 positive blood vessels were increased at the site of ischemic white matter lesions. We revealed that ROCK1 or RhoB positive blood vessels increase in hippocampus where accumulation of Aβ occurs, and LIM-kinase 2 positive blood vessels increase around hippocampus in Alzheimer's disease model mice. ROCK1 positive blood vessels were also found on the brain surface. The ROCK inhibitor Fasudil was administered to the rat model of vascular dementia. It was revealed that Fasudil has an inhibitory effect on the increase in the number of blood vessels with ROCK1 or RhoB positive. Fasudil has the protective effect against the ischemic white matter lesions.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

本研究で血管性認知症におけるRho-ROCKシグナルの役割が解明され、血管性認知症における、今までにない新規の病態機序の分子メカニズムが提示された。本成果は、血管性認知症研究の発展に貢献すると考えられる。ROCK阻害剤投与により脳病変の抑止効果が認められ、血管性認知症の予防・治療法への臨床応用という点においても意義あるものとなる。また、アルツハイマー病のアミロイド排出機序とRho-ROCKシグナルの関連を解明した。本成果は、アルツハイマー病研究の発展に貢献するととともに、予防・治療法開発につながる成果でもある。