{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:04:19Z","timestamp":1760238259720,"version":"build-2065373602"},"reference-count":36,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T00:00:00Z","timestamp":1595808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI14C2746, HI18C0335020119"],"award-info":[{"award-number":["HI14C2746, HI18C0335020119"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018M3C7A1056894"],"award-info":[{"award-number":["NRF-2018M3C7A1056894"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"iPS Bio, Inc.","award":["Internal funding"],"award-info":[{"award-number":["Internal funding"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Frontotemporal dementia (FTD) is caused by the progressive degeneration of the frontal and temporal lobes of the brain. Behavioral variant FTD (bvFTD) is the most common clinical subtype of FTD and pathological subtypes of bvFTD are known as FTD-tau, transactive response (TAR) DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS). Pathological mechanisms of bvFTD are largely unknown. In this study, we investigated the expression of pathological markers, such as p-Tau, TDP-43, and FUS, in the induced pluripotent stem-cell-derived neurons (iPSN) from two sporadic bvFTD patients and one normal subject. We also used an FTD-patient-derived iPSC-line-carrying microtubule-associated protein tau (MAPT) P301L point mutation as positive control for p-Tau expression. Staurosporine (STS) was used to induce cellular stress in order to investigate dynamic cellular responses related to the cell death pathway. As a result, the expression of active caspase-3 was highly increased in the bvFTD-iPSNs compared with control iPSNs in the STS-treated conditions. Other cell-death-related proteins, including Bcl-2-associated X protein (Bax)\/Bcl-2 and cytochrome C, were also increased in the bvFTD-iPSNs. Moreover, we observed abnormal expression patterns of TDP-43 and FUS in the bvFTD-iPSNs compared with control iPSNs. We suggest that the iPSC technology might serve as a potential tool to demonstrate neurodegenerative phenotypes of bvFTD, which will be useful for studying pathological mechanisms for FTD as well as related drug screening in the future.<\/jats:p>","DOI":"10.3390\/ijms21155319","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:16:49Z","timestamp":1595931409000},"page":"5319","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Modeling of Frontotemporal Dementia Using iPSC Technology"],"prefix":"10.3390","volume":"21","author":[{"given":"Minchul","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wonyoung","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyohoon","family":"Heo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul Hyoung","family":"Lyoo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 06273, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Won","family":"Seo","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Joo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan 49241, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahito","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"TOKIWA-Bio, Inc., Tsukuba Center Inc. (TCI), Building G, 2-1-6 Sengen, Tsukuba, Ibaraki 305-0047, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duk L.","family":"Na","sequence":"additional","affiliation":[{"name":"Neuroscience Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Samsung Alzheimer Research Center, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"},{"name":"Stem Cell &amp; Regenerative Medicine Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6597-8208","authenticated-orcid":false,"given":"Jihwan","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea"},{"name":"iPS Bio, Inc., Rm 302-8, 26 Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13522, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1055\/s-0034-1381735","article-title":"Frontotemporal lobar degeneration: A clinical approach","volume":"34","author":"Karageorgiou","year":"2014","journal-title":"Semin. 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