Analyzing the pathogenesis of neurodegenerative diseases using medaka with multigene mutations.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670442
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Kyoto University
• Principal Investigator: Takahashi Ryosuke 京都大学, 医学(系)研究科(研究院), 教授 (90216771)
• Co-Investigator(Renkei-kenkyūsha): UEMURA Norihito 京都大学, 大学院医学研究科, 特定助教 (90749045)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: パーキンソン病 / メダカ / α‐シヌクレイン / GBA

Outline of Final Research Achievements

Parkinson’s disease (PD) is pathologically characterized by dopaminergic neuron loss and intraneuronal α-synuclein (α-syn) aggregates. Recent genetic studies have revealed that GBA mutations confer a strong risk for PD. In the present study, we generated and analyzed GBA nonsense mutant (GBA－/－) medaka. In contrast to the perinatal death in other species lacking GBA, GBA－/－ medaka survived for months, enabling analysis of the pathological progression. Pathological findings represented α-syn accumulation in their brains, which was caused by the impairment of autophagy-lysosome pathway. Furthermore, we generated α-syn deletion mutant medaka and human α-syn transgenic medaka. We crossed them with GBA mutant medaka respectively, but these double mutant medaka did not displayed any pathological changes. From these results, this study could not elucidate the pathological role of α-syn in GBA－/－ medaka.

Free Research Field

神経内科学