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Article

Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs

1
Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea
2
Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, Korea
3
Department of Dental Pharmacology, School of Dentistry, BK21 Plus, Jeonbuk National University, Jeonju 54896, Korea
4
Division of Herbal Medicine Research, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea
5
Division of Clinical Medicine, Korea Institute of Oriental Medicine (KIOM), 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Korea
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Life 2020, 10(12), 331; https://doi.org/10.3390/life10120331
Received: 19 October 2020 / Revised: 27 November 2020 / Accepted: 3 December 2020 / Published: 7 December 2020
(This article belongs to the Section Proteins and Proteomics)
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 G2019S 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. View Full-Text
Keywords: Parkinson’s disease; pNSCs; LRRK2; proteomic analysis; Ku80; DNA damage response Parkinson’s disease; pNSCs; LRRK2; proteomic analysis; Ku80; DNA damage response
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MDPI and ACS Style

Sim, H.; Seo, J.-H.; Kim, J.; Oh, M.; Lee, J.-E.; Baek, A.; Lee, S.-Y.; Chung, S.-K.; Son, M.-Y.; Chae, J.-I.; Jeon, Y.-J.; Kim, J. Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs. Life 2020, 10, 331. https://doi.org/10.3390/life10120331

AMA Style

Sim H, Seo J-H, Kim J, Oh M, Lee J-E, Baek A, Lee S-Y, Chung S-K, Son M-Y, Chae J-I, Jeon Y-J, Kim J. Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs. Life. 2020; 10(12):331. https://doi.org/10.3390/life10120331

Chicago/Turabian Style

Sim, Hyuna, 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, and Janghwan Kim. 2020. "Quantitative Proteomic Analysis of Primitive Neural Stem Cells from LRRK2 G2019S-Associated Parkinson’s Disease Patient-Derived iPSCs" Life 10, no. 12: 331. https://doi.org/10.3390/life10120331

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