Development of novel cellular models for Parkinson's disease focusing on energy-homeostasis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09676
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: FUNAYAMA Manabu 順天堂大学, 医学部, 准教授 (70468578)
• Research Collaborator: AMO taku ; AKAMATSU wado
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: パーキンソン病 / ミトコンドリア / 電子伝達系 / 遺伝子 / iPS細胞 / ノックアウト細胞 / 酸化ストレス

Outline of Final Research Achievements

We recently identified coiled-coil-helix coiled-coil-helix domain containing 2 (CHCHD2) mutations are novel causes for autosomal dominant Parkinson’s disease (PD). Although CHCHD2 is localized to mitochondria and involved in mitochondrial complex IV, its function remains largely unknown. To elucidate the role of CHCHD2 in mitochondria, we generated CHCHD2 knockout SH-SY5Y neuroblastoma cells (CHCHD2-KO) and induced pluripotent stem cells (iPSc) derived from PD patient with CHCHD2 T61I mutation.
CHCHD2-KO as well as iPS showed a profound mitochondrial dysfunction, suggesting that CHCHD2 plays a crucial role in maintaining normal mitochondrial function. These findings indicate that CHCHD2 cellular models are a useful model for understanding CHCHD2 function and pathophysiology of CHCHD2 mutations and PD.

Free Research Field

人類遺伝学

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病 (PD) とミトコンドリア機能低下は数十年来指摘されているが、家族性PDの原因遺伝子で直接ミトコンドリア電子伝達系に関与している遺伝子はCHCHD2のみである。本研究で開発したCHCHD2細胞モデル (ノックアウト細胞およびPD患者iPS細胞) に共通してミトコンドリア電子伝達系の機能低下が見出され、この表現型を指標としたPDの病態解明や新規治療薬の開発への貢献が期待される。