Elucidation of the mechanisms of the Parkinson's disease genes and Lewy Body formation and alpha-synuclein propagation mechanisms

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H04043
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Juntendo University
• Principal Investigator: Hattori Nobutaka 順天堂大学, 医学(系)研究科(研究院), 教授 (80218510)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: パーキンソン病 / α-シヌクレイン / SNCA / Lewy小体 / ミトコンドリア / オートファジー / CHCHD2 / PLA2G6

Outline of Final Research Achievements

In models of CHCHD2 knockout flies, knockout mice, and patient-derived iPS cells, mitochondrial function declines in an age-dependent manner, forming SNCA-positive Lewy body-like inclusion bodies. Furthermore, analysis of PLA2G6 knockout flies showed shortening of the acyl group of brain phospholipids. It was clarified that the homeostasis of mitochondrial protein and phospholipid composition is the primary cause of the mechanism of aggregate formation in Parkinson's disease.

Free Research Field

神経内科

Academic Significance and Societal Importance of the Research Achievements

封入体を形成する遺伝性パーキンソン病に着目し、モデル動物の解析により封入体形成のメカニズム解明に迫ることができた。本研究の成果は多くを占める孤発性パーキンソン病の病態解明につながるものであり、今後の疾患予防や治療法開発に向けて基礎的な知見となる。