Reveal the mechanisms of aSyn transmission via exosome in PD patients

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16122
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: Ikenaka Kensuke 大阪大学, 医学系研究科, 助教 (70774058)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: パーキンソン病 / alpha synuclein / 伝播 / エクソソーム

Outline of Final Research Achievements

Endoplasmic reticulum-associated protein A was identified by analyzing the protein increased in exosomes when synuclein fibrils were highly expressed.
Overexpression of protein A increased the extracellular release of aSyn via exosomes. In addition, immunoprecipitation showed that αSyn was directly bound to protein A.Interestingly, when αSyn itself was overexpressed while protein A was overexpressed, αSyn-positive inclusion bodies were confirmed in the cells.
When comparing the amount of αSyn in exosomes when co-expressing protein A with fibril or monomer of αSyn pathogenic mutation, the G51D mutation was very strongly incorporated to exosome.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

本研究では、αシヌクレインというパーキンソン病の発病原因の最も中核にある分子の一つが、どのように細胞から細胞に伝播していくか、その様式の一助を明らかにした。蛋白質Aの増加がパーキンソン病患者において特異的に、または加齢に伴い非特異的に、増加している場合、蛋白質Aの発現を押さえる治療がパーキンソン病の進展を予防する効果が期待できる。