α-Synuclein Aggregation and Propagation in the Pathomechanisms of Parkinson’s Disease

抄録

Parkinson’s disease is a neurodegenerative disorder that manifests with motor dysfunction, such as bradykinesia, tremor, and rigidity. Furthermore, patients experience many non-motor problems, including dementia, psychosis, pain, sleep disturbances, and autonomic dysfunction, which impact their quality of life. Thus, disease-modifying therapies for Parkinson’s disease are needed. The pathological hallmark of this disease is dopaminergic neuronal loss with intraneuronal aggregations, known as Lewy bodies, which contain proteins and lipids. Recently, it was revealed that several membranous organelles, such as mitochondria, lysosomes, autophagosomes, and synaptic vesicles, are involved in Lewy bodies. Moreover, the main protein component of Lewy body, α-synuclein, binds to lipid membranes via two α-helices at the N-terminus. Interestingly, disrupted associations between lipid membranes and α-synuclein might trigger the formation of Lewy body. Accordingly, α-synuclein aggregation and lipid-synuclein interactions are important for the pathomechanisms of Parkinson’s disease. In this review, I will focus on (1) the role of lipid metabolism in Parkinson’s disease, and (2) α-synuclein aggregation and propagation in Parkinson’s disease.