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Typical of PD pathology is the finding of protein aggregations termed \u2018Lewy bodies\u2019 in the brain regions affected. \u03b1-synuclein is implicated in many disease states including dementia with Lewy bodies (DLB) and Alzheimer\u2019s disease. However, PD is the most common synucleinopathy and continues to be a significant focus of PD research in terms of the \u03b1-synuclein Lewy body pathology. Mutations in several genes are associated with PD development including SNCA, which encodes \u03b1-synuclein. A variety of model systems have been employed to study \u03b1-synuclein physiology and pathophysiology in an attempt to relate more closely to PD pathology. These models include cellular and animal system exploring transgenic technologies, viral vector expression and knockdown approaches, and models to study the potential prion protein-like effects of \u03b1-synuclein. The current review focuses on human induced pluripotent stem cell (iPSC) models with a specific focus on mutations or multiplications of the SNCA gene. iPSCs are a rapidly evolving technology with huge promise in the study of normal physiology and disease modeling in vitro. The ability to maintain a patient\u2019s genetic background and replicate similar cell phenotypes make iPSCs a powerful tool in the study of neurological diseases. This review focuses on the current knowledge about \u03b1-synuclein physiological function as well as its role in PD pathogenesis based on human iPSC models.<\/jats:p>","DOI":"10.1042\/ns20210021","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T13:27:14Z","timestamp":1623763634000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["\u03b1-synuclein pathogenesis in hiPSC models of Parkinson\u2019s disease"],"prefix":"10.1042","volume":"5","author":[{"given":"Jara\u00a0M.","family":"Baena-Montes","sequence":"first","affiliation":[{"name":"Physiology School of Medicine, National University of Ireland Galway, Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7705-8970","authenticated-orcid":false,"given":"Sahar","family":"Avazzadeh","sequence":"additional","affiliation":[{"name":"Physiology School of Medicine, National University of Ireland Galway, Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4011-6732","authenticated-orcid":false,"given":"Leo\u00a0R.","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Physiology School of Medicine, National University of Ireland Galway, Galway, Ireland"},{"name":"C\u00daRAM SFI Centre for Research in Medical Devices, National University of Ireland Galway, Galway, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"2021111608033603600_B1","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/B978-0-12-416002-6.00003-1","article-title":"Animal models for neurodegenerative disorders","volume-title":"Animal Biotechnology","author":"Tsuiji","year":"2014"},{"key":"2021111608033603600_B2","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.pneurobio.2015.07.003","article-title":"Protein aggregation and neurodegeneration in prototypical neurodegenerative diseases: examples of amyloidopathies, tauopathies and synucleinopathies","volume":"155","author":"Bourdenx","year":"2017","journal-title":"Prog. 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