Elucidation of the pathogenic mechanism of progression of Parkinson's disease using a primate genetic modification model

2018 Fiscal Year Final Research Report

• Project/Area Number: 16KT0193
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: Kyoto University
• Principal Investigator: Inoue Kenichi 京都大学, 霊長類研究所, 助教 (90455395)
• Research Collaborator: TAKATA MASAHIKO ; NINOMIYA TAIHEI
• Project Period (FY): 2016-07-19 – 2019-03-31
• Keywords: 神経科学 / 脳神経疾患 / パーキンソン / ウイルスベクター / 霊長類

Outline of Final Research Achievements

In the present study, by using viral vectors, we developed a novel macaque Parkinson's disease model (alpha-synuclein overexpression model) in which progressive neurodegeneration persisted for more than several months. We also developed a tyrosine hydroxylase promoter with relatively high selectivity for dopamine cells and efficient transgene expression. In addition, we have developed and performed various analyses of Parkinson's disease models, including behavioral, histological, and biochemical analyses, as well as brain function image and electrophysiological analyses. In these experiments, we have obtained some new findings about the the pathogenic mechanism of progression of Parkinson's disease, such as changes in the concentrations of various enzymes in cerebrospinal fluid, the dynamics of oscillation in the brain including synchronization between fields, and the inhibitory effect of calcium-binding protein on the progression of the disease.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

症状発症時には８割もの黒質ドーパミン神経細胞が細胞死を起こしているパーキンソン病の根治治療には、無症状だが脳内で病態が進行している状態を検出し、その進行を止めるための治療を行うことが極めて重要となる。ヒトの病態進行と近い進行性の黒質ドーパミン細胞の神経変性を示すマカクザルパーキンソン病モデルの開発という本研究の成果は、パーキンソン病の病態機序の理解に大きく寄与できるほか、このモデル動物において経時的に本研究で一部開発した様々な解析法によるデータを取得することにより、病態の進行様式や疾病の発症機序の解明や、病態の段階を検出しうるマーカーの開発が進むことが期待される。