Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs
Parkinson’s disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been...
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MDPI AG
2020-12-01
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| Online Access: | https://www.mdpi.com/2075-1729/10/12/331 |
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| author | Hyuna Sim Ji-Hye Seo Jumi Kim Minyoung Oh Joo-Eun Lee Areum Baek Seo-Young Lee Sun-Ku Chung Mi-Young Son Jung-Il Chae Young-Joo Jeon Janghwan Kim |
| author_facet | Hyuna Sim Ji-Hye Seo Jumi Kim Minyoung Oh Joo-Eun Lee Areum Baek Seo-Young Lee Sun-Ku Chung Mi-Young Son Jung-Il Chae Young-Joo Jeon Janghwan Kim |
| author_sort | Hyuna Sim |
| collection | DOAJ |
| description | Parkinson’s disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 <i>G2019S</i> mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD. |
| first_indexed | 2024-03-10T14:16:33Z |
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| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T14:16:33Z |
| publishDate | 2020-12-01 |
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| series | Life |
| spelling | doaj.art-68bbf5eeed474bf98f8057149e067b4b2023-11-20T23:45:32ZengMDPI AGLife2075-17292020-12-01101233110.3390/life10120331Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCsHyuna Sim0Ji-Hye Seo1Jumi Kim2Minyoung Oh3Joo-Eun Lee4Areum Baek5Seo-Young Lee6Sun-Ku Chung7Mi-Young Son8Jung-Il Chae9Young-Joo Jeon10Janghwan Kim11Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaDepartment of Dental Pharmacology, School of Dentistry, BK21 Plus, Jeonbuk National University, Jeonju 54896, KoreaDepartment of Dental Pharmacology, School of Dentistry, BK21 Plus, Jeonbuk National University, Jeonju 54896, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaDivision of Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, KoreaDivision of Clinical Medicine, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaDepartment of Dental Pharmacology, School of Dentistry, BK21 Plus, Jeonbuk National University, Jeonju 54896, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaStem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, KoreaParkinson’s disease (PD) is a common neurodegenerative disease, causing movement defects. The incidence of PD is constantly increasing and this disease is still incurable. Thus, understanding PD pathophysiology would be pivotal for the development of PD therapy, and various PD models have thus been already developed. Through recent advances in reprogramming techniques, a primitive neural stem cell (pNSC) derived from PD patient induced pluripotent stem cells (iPSCs) could be potentially used as a reproducible and reliable experimental system to analyze the effect of the leucine-rich repeat kinase 2 <i>G2019S</i> mutation (LK2GS) in neural cells. Here, we investigated the advantages of such a model system through quantitative proteomic analysis of pNSCs from normal control iPSCs and familial PD patient iPSCs harboring LK2GS. We confirmed that the expression of molecules known to be involved in PD pathogenesis, such as oxidative stress-, cell adhesion-, and cytoskeleton-related proteins, were altered in the LK2GS pNSC. In addition, we showed that down-regulation of Ku80, which was found in the proteomic analysis with LK2GS pNSCs, resulted in apoptosis induced by DNA damage response. Taken together, we suggest that pNSCs from PD iPSCs could provide a reliable and useful model system to study PD. Moreover, the highly expandable pNSC is suitable for multi-omics approaches to understand PD pathologies and discover therapeutic targets for PD.https://www.mdpi.com/2075-1729/10/12/331Parkinson’s diseasepNSCsLRRK2proteomic analysisKu80DNA damage response |
| spellingShingle | Hyuna Sim Ji-Hye Seo Jumi Kim Minyoung Oh Joo-Eun Lee Areum Baek Seo-Young Lee Sun-Ku Chung Mi-Young Son Jung-Il Chae Young-Joo Jeon Janghwan Kim Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs Life Parkinson’s disease pNSCs LRRK2 proteomic analysis Ku80 DNA damage response |
| title | Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs |
| title_full | Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs |
| title_fullStr | Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs |
| title_full_unstemmed | Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs |
| title_short | Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs |
| title_sort | quantitative proteomic analysis of primitive neural stem cells from lrrk2 g2019s associated parkinson s disease patient derived ipscs |
| topic | Parkinson’s disease pNSCs LRRK2 proteomic analysis Ku80 DNA damage response |
| url | https://www.mdpi.com/2075-1729/10/12/331 |
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