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534SNARE protein, prevented the propagation of α-synuclein. Thus, synaptic exocytosis might be one mechanism by which transmission of α-synu-clein fibrils occurs.ConclusionThis review focused on the aggregation and propagation of α-synuclein in the pathomechanism of Parkinson’s disease. However, previous reports have indicated the importance of other pathogenic systems in Parkinson’s disease, such as protein degradation, mitochondrial dysfunction, neuroin-flammation, and ER stress49). Considering that many membranous organelles, such as mitochon-dria, autophagosomes, lysosomes, and synaptic vesicles, are involved with Lewy bodies, multiple dysfunctions in neurons and/or glial cells may contribute to the neurodegeneration in Parkinson’s disease (Figure 1). Thus, to reveal the key event in the pathogenesis of Parkinson’s disease, further investigation should be needed.Figure 1　α-Synuclein, an amphipathic protein, contains two N-terminal α-helices that are important for binding to the membrane. In the cytosol, α-synuclein moves dynamically and does not have specific structure. The conformational alteration of α-synuclein, which includes β-sheet structures, is associated with self-aggregation. Disruptions of interaction between α-synuclein and lipid membranes due to pathogenic α-synuclein mutations and/or dysregulated phospholipid and glycolipid metabolism may induce conformational changes of α-synuclein. Correlative light and electron microscopy revealed that Lewy bodies involve many types of organelles, such as mitochondria, lysosomes, autophagosomes, membranes, and synaptic vesicles. Thus, aggregation of α-synuclein will induce many abnormalities of cellular function. Furthermore, α-synuclein seeds will propagate along the neuronal circuit, resulting in the systemic α-synuclein aggregations observed in Parkinson’s disease.The author thanks Drs. Nobutaka Hattori, Yuzuru Imai, Yutaka Oji, Akio Mori, Ayami Okuzumi Shiu-ichi Ueno (from Juntendo Univer-sity Faculty of Medicine), Nobuyuki Nukina (from Doshisha University), and Junko Matsuda (from Kawasaki Medical University). The author thanks Edanz Group (https://jp.edanz.com/ac) for editing a draft of this manuscript. This study was supported by the Japan Agency for Medical Research and Development (Grant Nos. 21wm0425015, 21dk0207055, and 20dm0107156), Japan Society for the Promotion of Science (KAKENHI, Grant No. 21K07424), and Setsuro Fujii Memorial Osaka Foundation for Promotion of Fundamental Medical Research.AcknowledgementsFunding