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CS has been associated with mutations in the <jats:italic>VPS13B<\/jats:italic> (vacuolar protein sorting 13 homolog B) gene, which regulates vesicle-mediated protein sorting and transport; however, the cellular mechanism underlying CS pathogenesis in patient-derived neurons remains uncertain. This report states that autophagic vacuoles accumulate in CS fibroblasts and the axonal terminals of CS patient-specific induced pluripotent stem cells (CS iPSC)-derived neurons; additionally, autophagic flux was significantly increased in CS-derived neurons compared to control neurons. <jats:italic>VPS13B<\/jats:italic> knockout HeLa cell lines generated using the CRISPR\/Cas9 genome editing system showed significant upregulation of autophagic flux, indicating that <jats:italic>VSP13B<\/jats:italic> may be associated with autophagy in CS. Transcriptomic analysis focusing on the autophagy pathway revealed that genes associated with autophagosome organization were dysregulated in CS-derived neurons. <jats:italic>ATG4C<\/jats:italic> is a mammalian ATG4 paralog and a crucial regulatory component of the autophagosome biogenesis\/recycling pathway. <jats:italic>ATG4C<\/jats:italic> was significantly upregulated in CS-derived neurons, indicating that autophagy is upregulated in CS neurons. The autophagy pathway in CS neurons may be associated with the pathophysiology exhibited in the neural network of CS patients.<\/jats:p>","DOI":"10.1186\/s13041-020-00611-7","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T12:04:25Z","timestamp":1588766665000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Autophagy pathway upregulation in a human iPSC-derived neuronal model of Cohen syndrome with VPS13B missense mutations"],"prefix":"10.1186","volume":"13","author":[{"given":"You-Kyung","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Kyeong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suin","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Hoon","family":"Huh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Hye","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Seok","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deok-Jin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungmin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bong-Kiun","family":"Kaang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chae-Seok","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6757-8371","authenticated-orcid":false,"given":"Jin-A","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,6]]},"reference":[{"issue":"3","key":"611_CR1","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1016\/j.ygeno.2004.04.012","volume":"84","author":"A Velayos-Baeza","year":"2004","unstructured":"Velayos-Baeza A, Vettori A, Copley RR, Dobson-Stone C, Monaco AP. Analysis of the human VPS13 gene family. Genomics. 2004;84(3):536\u201349.","journal-title":"Genomics"},{"issue":"4","key":"611_CR2","doi-asserted-by":"publisher","first-page":"275","DOI":"10.18388\/pb.2018_141","volume":"64","author":"J Kaminska","year":"2018","unstructured":"Kaminska J, Kolakowski D. Proteins from Vps13 family: from molecular function to pathogenesis of neurodegenerative disorders. Postepy Biochem. 2018;64(4):275\u201387.","journal-title":"Postepy Biochem"},{"issue":"4","key":"611_CR3","doi-asserted-by":"publisher","first-page":"485","DOI":"10.5607\/en.2019.28.4.485","volume":"28","author":"MJ Kim","year":"2019","unstructured":"Kim MJ, Lee RU, Oh J, Choi JE, Kim H, Lee K, Hwang S-K, Lee J-H, Lee J-A, Kaang B-K. Spatial learning and motor deficits in vacuolar protein sorting-associated protein 13b (Vps13b) mutant mouse. 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