Chorea-acanthocytosis and mitophagy: clarifying the molecular mechanisms of the disease and developing methods to prevent neurodegeneration

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04250
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Kagoshima University
• Principal Investigator: Sano Akira 鹿児島大学, 医歯学域医学系, 教授 (30178800)
• Co-Investigator(Kenkyū-buntansha): 中村 雅之 鹿児島大学, 医歯学域医学系, 准教授 (90332832)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 有棘赤血球舞踏病 / マイトファジー

Outline of Final Research Achievements

Selective autophagy for impaired mitochondria is known as mitophagy, by which mitochondrial quality is preserved. Chorein, a protein responsible for chorea-acanthocytosis, was suggested to be involved in mitophagy-mediated mitochondrial quality control mechanisms. It was suggested that the neurodegeneration in chorea-acanthocytosis may be due in part to a disruption of mitophagy.
We found that patients with chorea-acanthocytosis exhibited a variety of psychiatric symptoms, including cognitive decline. Approximately 55% of the mutations in Japanese patients with ChAc carried two major mutations. These mutations were localized in Tokyo and west side of Japan and the partial founder effects were suggested.

Free Research Field

分子精神神経医学

Academic Significance and Societal Importance of the Research Achievements

有棘赤血球舞踏病は、国際的には日本人に多いとされる稀な遺伝性神経変性疾患である。今回の研究で、有棘赤血球舞踏病が認知機能障害を含む多彩な精神症状を呈することが明らかとなった。また、有棘赤血球舞踏病の病因にミトコンドリアの品質維持機構の破綻が関与している可能性が示唆された。有棘赤血球舞踏病が多彩な精神症状を呈することからも、choreinとマイトファジーが他の精神神経疾患と関連する可能性と、その破綻した機構の回復が多くの精神神経疾患の分子的な治療の一端となる可能性がある。