The mechanism of alpha-synuclein propagation

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16610
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Taruno Yosuke 京都大学, 医学研究科, 客員研究員 (40817235)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: αシヌクレイン / 伝播 / 神経活動

Outline of Final Research Achievements

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease (AD). PD is pathologically characterized by Lewy bodies, which are aggregates of α-synuclein (α-Syn). Although it is now known that α-Syn aggregates amplify and propagate from neuron to neuron one after another like prion proteins, little is known about the mechanism by which this propagation occurs. In this study, we experimentally confirmed that the propagation of α-Syn aggregates is altered by suppressing neuronal activity. We inoculated α-Syn aggregates into the olfactory bulb of mice and closed the ipsilateral nasal cavity to suppress neural activity induced by olfactory stimulation. Based on these data on the relationship between neural activity and the propagation of α-Syn aggregates, we investigated whether the propagation of α-Syn aggregates could be suppressed by suppressing neural activity with drugs, and reported the results in a paper (Mov Disord, 2021).

Free Research Field

臨床神経学

Academic Significance and Societal Importance of the Research Achievements

神経活動とαシヌクレイン伝播の関連性を明らかとし、ペランパネルによるαシヌクレイン伝播の進展抑制の可能性を示した。この結果はαシヌクレイン伝播の機序を解明するだけではなく、パーキンソン病の疾患修飾薬としてペランパネルが使用できる可能性を示した。さらにその他の神経活動に関連した薬剤についても疾患修飾薬として使用できる可能性も示された。