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2021 Fiscal Year Final Research Report

Elucidation of the pathomechanism of neurodegenerative diseases by comparing the causative proteins between species

Research Project

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Project/Area Number 18H02338
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionThe University of Tokyo

Principal Investigator

Chambers James  東京大学, 大学院農学生命科学研究科(農学部), 助教 (00621682)

Co-Investigator(Kenkyū-buntansha) 内田 和幸  東京大学, 大学院農学生命科学研究科(農学部), 准教授 (10223554)
Project Period (FY) 2018-04-01 – 2022-03-31
Keywords神経変性疾患 / 生物種差 / プロテイノパシー / β-amyloid / α-synuclein / Tau
Outline of Final Research Achievements

Causative proteins of neurodegenerative diseases and their associated lesions were examined in animal brains and compared between different species. Lesions comparable to human Alzheimer's disease were found in the brains of sea lions and other several species. We found that the nature of the proteins, such as amino acid sequence, expressed isoforms, and aggregability, were associated with different lesions in the brain among species. Also, results of experimental studies have shown that different causative proteins interact with each other via activation of kinase, and promote lesion formation.

Free Research Field

獣医病理学

Academic Significance and Societal Importance of the Research Achievements

アルツハイマー病などの神経変性疾患では、脳の神経細胞内に蛋白質の凝集がみられるが、その原因は解明されていない。本研究では、それらの蛋白質のアミノ酸配列に生物種差があり、病変形成と関連していることを明らかにした。また、2種類の蛋白質が相互作用し、それぞれの凝集を促進することを実験的に明らかにした。すなわち、神経細胞内の蛋白質凝集性は、進化の過程で生物種ごとに規定されており、それらの蛋白質の相互作用をコントロールすることが疾患の予防および進行の抑制に重要であると考えられた。

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Published: 2023-01-30  

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