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2022 Fiscal Year Final Research Report

Characterization of disease-specific variants of the mitochondrial protein CHCHD2

Research Project

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Project/Area Number 20K07361
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49010:Pathological biochemistry-related
Research InstitutionJuntendo University

Principal Investigator

Meng Hongrui  順天堂大学, 医学部, 非常勤助教 (90736498)

Project Period (FY) 2020-04-01 – 2023-03-31
Keywordsパーキンソン病 / 筋萎縮性側索硬化症 / ショウジョウバエ / ミトコンドリア / α-Synuclein / TDP-43
Outline of Final Research Achievements

New missense variants of the late-onset Parkinson's disease (PD) causative gene CHCHD2 were found in amyotrophic lateral sclerosis (ALS) case. The CHCHD2 ALS variant, like the PD variant, failed to improve mitochondrial degeneration in CHCHD2 knockout flies, suggesting that it is a pathogenic mutation. One of the ALS variants tended to localize to the cytoplasm and has impaired mitochondrial Ca2+ buffering ability, possibly leading to calcium toxicity. In contrast, the PD variant was found to aggregate within mitochondria and become insoluble with its binding partner CHCHD10. Different properties of these variants may contribute to the pathogenesis of different neurodegenerative diseases.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病(PD)と筋萎縮性側索硬化症(ALS)は神経細胞内に異常タンパク質の封入体が認められる神経変性疾患である。これら2つの神経変性疾患については多くの原因遺伝子が同定されているが、同一の遺伝子がPDとALSの両方の原因となる例はCHCHD2が初めてである。一つの遺伝子が2種類の神経変性疾患の原因となる分子機序を明らかにすることにより、両疾患の共通の創薬標的を同定することに繋がると期待される。

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Published: 2024-01-30  

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