Histone modification induced by alpha-synuclein

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09745
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tohoku University
• Principal Investigator: Sugeno Naoto 東北大学, 大学病院, 助教 (30509550)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: パーキンソン病 / エピジェネティクス / αーシヌクレイン

Outline of Final Research Achievements

Alpha-synuclein (aS) is a key molecule to understand pathomechanisms underlying Parkinson’s disease. Physiological intracellular localization of aS is mainly pre-synaptic membrane, but a part of aS reside nucleus. We focused on the function of aS in nucleus, especially in epigenomic regulation of neuronal genes. At the first step of this project, we tried to find out the aS-interacting proteins in nucleus, and successfully achieved because some of the components of BAF complex that actively work during neuronal differentiation, were significantly bonded with aS. Also, the enzyme that catalyzes histone methylation was also involve in this complex. Interestingly, altered histone modification targeted by the enzyme was enhanced by aS expression in differentiated SH-SY5Y cells. Finally, we identified some neuronal genes affected by the histone methylation.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病発症の最大のリスクは加齢であり、現在進行中の高齢化社会において本疾患への対応は急務となっている。ドパミン補充療法が運動機能改善に役立つものの、一方でドパミン製剤による衝動制御障害は罹患者の生活を破壊しうるものであり発生を未然に防ぐ必要がある。本研究ではαシヌクレインを出発点とした分子生物学的アプローチにより、衝動制御障害のリスクとなりうる遺伝子の発現変化が導かれることを見出した。今後、実臨床へと発展させることにより衝動制御障害のリスクを事前に知ることが可能となると思われる。