exploring new pathways of alpha-synuclein propagation in Parkinson's Disease

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K20691
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0704:Neuroscience, brain sciences, and related fields
• Research Institution: Kyoto University
• Principal Investigator: Taguchi Tomoyuki 京都大学, 医学研究科, 特定助教 (00909393)
• Project Period (FY): 2021-08-30 – 2024-03-31
• Keywords: パーキンソン病 / αシヌクレイン / 進展経路 / 末梢血単核細胞

Outline of Final Research Achievements

The leading hypothesis for the onset and progression of Parkinson's disease (PD) suggests that aggregated α-synuclein (α-syn) starts in the gut and ascends to the central nervous system via the vagus nerve. However, studies on autopsied PD brains show that not all cases follow this pattern. In this study, we explored a new potential pathway for α-syn progression through peripheral immune cells. Our results indicated that while peripheral blood mononuclear cells (mainly CD11b-positive cells) that phagocytosed aggregated α-syn could enter the brain during systemic inflammation, this did not lead to the progression of α-syn pathology. These findings suggest that peripheral CD11b-positive cells have a high capacity to degrade aggregated α-syn, highlighting the potential for new therapies to inhibit α-syn aggregation.

Free Research Field

パーキンソン病

Academic Significance and Societal Importance of the Research Achievements

本研究は、パーキンソン病の病理進展メカニズムに対する新たな視点を提供し、従来の仮説を再評価するきっかけになったと考える。また末梢免疫細胞を応用した新たな治療法の開発につながる可能性を秘めていると言える。