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Modeling of Frontotemporal Dementia Using iPSC Technology

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...

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Autores principales: Kim, Minchul, Kim, Hee Jin, Koh, Wonyoung, Li, Ling, Heo, Hyohoon, Cho, Hanna, Lyoo, Chul Hyoung, Seo, Sang Won, Kim, Eun-Joo, Nakanishi, Mahito, Na, Duk L., Song, Jihwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432206/
https://www.ncbi.nlm.nih.gov/pubmed/32727073
http://dx.doi.org/10.3390/ijms21155319
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author Kim, Minchul
Kim, Hee Jin
Koh, Wonyoung
Li, Ling
Heo, Hyohoon
Cho, Hanna
Lyoo, Chul Hyoung
Seo, Sang Won
Kim, Eun-Joo
Nakanishi, Mahito
Na, Duk L.
Song, Jihwan
author_facet Kim, Minchul
Kim, Hee Jin
Koh, Wonyoung
Li, Ling
Heo, Hyohoon
Cho, Hanna
Lyoo, Chul Hyoung
Seo, Sang Won
Kim, Eun-Joo
Nakanishi, Mahito
Na, Duk L.
Song, Jihwan
author_sort Kim, Minchul
collection PubMed
description 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.
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spelling pubmed-74322062020-08-24 Modeling of Frontotemporal Dementia Using iPSC Technology Kim, Minchul Kim, Hee Jin Koh, Wonyoung Li, Ling Heo, Hyohoon Cho, Hanna Lyoo, Chul Hyoung Seo, Sang Won Kim, Eun-Joo Nakanishi, Mahito Na, Duk L. Song, Jihwan Int J Mol Sci Article 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. MDPI 2020-07-27 /pmc/articles/PMC7432206/ /pubmed/32727073 http://dx.doi.org/10.3390/ijms21155319 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kim, Minchul
Kim, Hee Jin
Koh, Wonyoung
Li, Ling
Heo, Hyohoon
Cho, Hanna
Lyoo, Chul Hyoung
Seo, Sang Won
Kim, Eun-Joo
Nakanishi, Mahito
Na, Duk L.
Song, Jihwan
Modeling of Frontotemporal Dementia Using iPSC Technology
title Modeling of Frontotemporal Dementia Using iPSC Technology
title_full Modeling of Frontotemporal Dementia Using iPSC Technology
title_fullStr Modeling of Frontotemporal Dementia Using iPSC Technology
title_full_unstemmed Modeling of Frontotemporal Dementia Using iPSC Technology
title_short Modeling of Frontotemporal Dementia Using iPSC Technology
title_sort modeling of frontotemporal dementia using ipsc technology
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432206/
https://www.ncbi.nlm.nih.gov/pubmed/32727073
http://dx.doi.org/10.3390/ijms21155319
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