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2018 Fiscal Year Final Research Report

The therapeutic strategy for amyotrophic lateral sclerosis by elucidation and removal of accumulated protein-cleaving factors

Research Project

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Project/Area Number 16K09681
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurology
Research InstitutionTeikyo University

Principal Investigator

TAKUMA Hiroshi  帝京大学, 医学部, 講師 (00326258)

Co-Investigator(Kenkyū-buntansha) 桜井 正樹  帝京大学, 医学部, 教授 (30162340)
郭 伸  東京大学, 大学院医学系研究科(医学部), 客員研究員 (40160981)
玉岡 晃  筑波大学, 医学医療系, 教授 (50192183)
塩谷 彩子  筑波大学, 医学医療系, 講師 (60622735)
前川 裕美  九州大学, 農学研究院, 講師 (80399683)
Research Collaborator KAMEDA Hiroshi  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords筋萎縮性側索硬化症 / 皮質運動野 / TDP-43 / microRNA
Outline of Final Research Achievements

In amyotrophic lateral sclerosis (ALS), many accumulated proteins and disease causative genes have been found, however the precise mechanism causing motor neuronal cell death has not been clarified, and we don’t get the path to ALS-treatment. In this study, TDP-43-related microRNAs obtained from model mice were not specifically altered in human ALS cerebral cortex motor cortex. In the comprehensive analysis of human motor area by microarray, we detected many microRNAs and mRNA candidates which expressions were changed, and a yeast system was also developed as a simple screening method for further study.

Free Research Field

神経内科学、分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

当初予定のin vivo電気穿孔法によるノックダウン・モデルマウスの開発には至らなかったが、ヒト脳におけるmicroRNAを含む遺伝子発現の網羅的データを得ることができた。これらの候補遺伝子の中には、ALSにおける神経変性の中核となる運動野において特異的に変化するものが多く含まれている。酵母による簡便なスクリーニング系も開発しており、今後の解析を通じて運動ニューロン死の実行役が同定されることが期待される。

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Published: 2020-03-30  

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