Quantitative proteomic analysis of primitive neural stem cells from LRRK2 G2019S-associated Parkinson's disease patient-derived iPSCs

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Title
Quantitative proteomic analysis of primitive neural stem cells from LRRK2 G2019S-associated Parkinson's disease patient-derived iPSCs
Author(s)
Hyuna Sim; J H Seo; J Kim; Minyoung Oh; Joo-Eun Lee; Areum Baek; S Y Lee; S K Chung; Mi-Young Son; J I Chae; Young Joo JeonJanghwan Kim
Bibliographic Citation
Life-Basel, vol. 10, no. 12, pp. 331-331
Publication Year
2020
Abstract
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.
Keyword
Parkinson’s diseasepNSCsLRRK2proteomic analysisKu80DNA damage response
ISSN
2075-1729
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/life10120331
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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