Emerging Disease-modifying Strategies Targeting α-synuclein in Parkinson's Disease Takafumi Hasegawa 1 , Junpei Kobayashi 1 , Shun Ishiyama 1 1Division of Neurology, Department of Neuroscience and Sensory Organs, Tohoku University Graduate School of Medicine Keyword: パーキンソン病 , αシヌクレイン , レヴィ小体 , 細胞間伝播 , 疾患修飾療法 , 抗体療法 , Parkinson's disease , α-synuclein , Lewy body , cell-to-cell transmission , disease-modifying treatment , antibody-based therapy pp.143-150
Published Date 2020/2/1
DOI https://doi.org/10.11477/mf.1416201494
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Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. Although the standard dopamine replacement therapy can alleviate motor symptoms, presently there is no available treatment to stop or reverse disease progression. Thus, there is an urgent need for the development of novel disease-modifying therapies to prevent the accumulation of cytotoxic α-synuclein (αS), a protein involved in PD pathogenesis, in the nervous system. Furthermore, emerging evidence suggests that the toxic αS species can move from one cell to another, thereby affecting the normal physiological state of the neighboring cells in a prion-like manner. The transmissible, extracellular αS is considered to be an ideal target for the disease-modifying treatments including antibody-based therapy. In this review, we will describe the molecular structure and functions of αS, its relevance to PD pathogenesis, and will discuss the current status and future perspectives of disease-modifying strategies targeting αS in PD.

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