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Lewy bodies (LBs), another histological hallmark of PD, are observed in patients with familial or sporadic PD. The therapeutic potential of reducing the accumulation of \u03b1\u2010synuclein, a major LB component, has been investigated, but it remains unknown whether the formation of LBs results in the loss of DA neurons. <jats:italic>PARK4<\/jats:italic> patients exhibit multiplication of the \u03b1\u2010synuclein gene (<jats:italic>SNCA<\/jats:italic>) without any pathological mutations, but their symptoms develop relatively early. Therefore, study of <jats:italic>PARK4<\/jats:italic> might help elucidate the mechanism of \u03b1\u2010synuclein aggregation. In this study, we investigated the dynamics of \u03b1\u2010synuclein during the early stage of immature DA neurons, which were differentiated from human\u2010induced pluripotent stem cells (hiPSCs) derived from either a <jats:italic>PARK4<\/jats:italic> patient with <jats:italic>SNCA<\/jats:italic> triplication or a healthy donor. We observed increased \u03b1\u2010synuclein accumulation in <jats:italic>PARK4<\/jats:italic> hiPSC\u2010derived DA neurons relative to those derived from healthy donor hiPSCs. Interestingly, \u03b1\u2010synuclein accumulation disappeared over time in the <jats:italic>PARK4<\/jats:italic> patient\u2010derived DA neurons. Moreover, an <jats:italic>SNCA<\/jats:italic>\u2010specific antisense oligonucleotide could reduce \u03b1\u2010synuclein levels during the accumulation stage. These observations may help reveal the mechanisms that regulate \u03b1\u2010synuclein levels, which may consequently be useful in the development of new therapies for patients with sporadic or familial PD.<\/jats:p>","DOI":"10.1002\/2211-5463.13060","type":"journal-article","created":{"date-parts":[[2020,12,11]],"date-time":"2020-12-11T03:18:31Z","timestamp":1607656711000},"page":"354-366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Alpha\u2010synuclein dynamics in induced pluripotent stem cell\u2010derived dopaminergic neurons from a Parkinson\u2019s disease patient (<i>PARK4<\/i>) with <i>SNCA<\/i> triplication"],"prefix":"10.1002","volume":"11","author":[{"given":"Hayato","family":"Fukusumi","sequence":"first","affiliation":[{"name":"Division of Stem Cell Research Department of Biomedical Research and Innovation Institute for Clinical Research National Hospital Organization Osaka National Hospital 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