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N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons
Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuro...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348654/ https://www.ncbi.nlm.nih.gov/pubmed/25735452 http://dx.doi.org/10.1038/srep08744 |
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author | Chang, Chia-Yu Chen, Sheng-Mei Lu, Huai-En Lai, Syu-Ming Lai, Ping-Shan Shen, Po-Wen Chen, Pei-Ying Shen, Ching-I Harn, Horng-Jyh Lin, Shinn-Zong Hwang, Shiaw-Min Su, Hong-Lin |
author_facet | Chang, Chia-Yu Chen, Sheng-Mei Lu, Huai-En Lai, Syu-Ming Lai, Ping-Shan Shen, Po-Wen Chen, Pei-Ying Shen, Ching-I Harn, Horng-Jyh Lin, Shinn-Zong Hwang, Shiaw-Min Su, Hong-Lin |
author_sort | Chang, Chia-Yu |
collection | PubMed |
description | Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles. |
format | Online Article Text |
id | pubmed-4348654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43486542015-03-10 N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons Chang, Chia-Yu Chen, Sheng-Mei Lu, Huai-En Lai, Syu-Ming Lai, Ping-Shan Shen, Po-Wen Chen, Pei-Ying Shen, Ching-I Harn, Horng-Jyh Lin, Shinn-Zong Hwang, Shiaw-Min Su, Hong-Lin Sci Rep Article Down syndrome (DS) patients with early-onset dementia share similar neurodegenerative features with Alzheimer's disease (AD). To recapitulate the AD cell model, DS induced pluripotent stem cells (DS-iPSCs), reprogrammed from mesenchymal stem cells in amniotic fluid, were directed toward a neuronal lineage. Neuroepithelial precursor cells with high purity and forebrain characteristics were robustly generated on day 10 (D10) of differentiation. Accumulated amyloid deposits, Tau protein hyperphosphorylation and Tau intracellular redistribution emerged rapidly in DS neurons within 45 days but not in normal embryonic stem cell-derived neurons. N-butylidenephthalide (Bdph), a major phthalide ingredient of Angelica sinensis, was emulsified by pluronic F127 to reduce its cellular toxicity and promote canonical Wnt signaling. Interestingly, we found that F127-Bdph showed significant therapeutic effects in reducing secreted Aβ40 deposits, the total Tau level and the hyperphosphorylated status of Tau in DS neurons. Taken together, DS-iPSC derived neural cells can serve as an ideal cellular model of DS and AD and have potential for high-throughput screening of candidate drugs. We also suggest that Bdph may benefit DS or AD treatment by scavenging Aβ aggregates and neurofibrillary tangles. Nature Publishing Group 2015-03-04 /pmc/articles/PMC4348654/ /pubmed/25735452 http://dx.doi.org/10.1038/srep08744 Text en Copyright © 2015, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chang, Chia-Yu Chen, Sheng-Mei Lu, Huai-En Lai, Syu-Ming Lai, Ping-Shan Shen, Po-Wen Chen, Pei-Ying Shen, Ching-I Harn, Horng-Jyh Lin, Shinn-Zong Hwang, Shiaw-Min Su, Hong-Lin N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title | N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title_full | N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title_fullStr | N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title_full_unstemmed | N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title_short | N-butylidenephthalide Attenuates Alzheimer's Disease-Like Cytopathy in Down Syndrome Induced Pluripotent Stem Cell-Derived Neurons |
title_sort | n-butylidenephthalide attenuates alzheimer's disease-like cytopathy in down syndrome induced pluripotent stem cell-derived neurons |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348654/ https://www.ncbi.nlm.nih.gov/pubmed/25735452 http://dx.doi.org/10.1038/srep08744 |
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