PMID- 32784741 OWN - NLM STAT- MEDLINE DCOM- 20210308 LR - 20210308 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 25 IP - 16 DP - 2020 Aug 7 TI - Neuroprotective Effects of Cryptotanshinone in a Direct Reprogramming Model of Parkinson's Disease. LID - 10.3390/molecules25163602 [doi] LID - 3602 AB - Parkinson's disease (PD) is a well-known age-related neurodegenerative disease. Considering the vital importance of disease modeling based on reprogramming technology, we adopted direct reprogramming to human-induced neuronal progenitor cells (hiNPCs) for in vitro assessment of potential therapeutics. In this study, we investigated the neuroprotective effects of cryptotanshinone (CTN), which has been reported to have antioxidant properties, through PD patient-derived hiNPCs (PD-iNPCs) model with induced oxidative stress and cell death by the proteasome inhibitor MG132. A cytotoxicity assay showed that CTN possesses anti-apoptotic properties in PD-hiNPCs. CTN treatment significantly reduced cellular apoptosis through mitochondrial restoration, such as the reduction in mitochondrial reactive oxygen species and increments of mitochondrial membrane potential. These effects of CTN are mediated via the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in PD-hiNPCs. Consequently, CTN could be a potential antioxidant reagent for preventing disease-related pathological phenotypes of PD. FAU - Lee, Joo-Eun AU - Lee JE AUID- ORCID: 0000-0002-2495-1439 AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. FAU - Sim, Hyuna AU - Sim H AUID- ORCID: 0000-0002-3051-8076 AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. AD - Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, Korea. FAU - Yoo, Hee Min AU - Yoo HM AUID- ORCID: 0000-0002-5951-2137 AD - Group for Biometrology, Korea Research Institute of Standards and Science (KRISS), Daejeon 34113, Korea. FAU - Lee, Minhyung AU - Lee M AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. FAU - Baek, Aruem AU - Baek A AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. FAU - Jeon, Young-Joo AU - Jeon YJ AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. FAU - Seo, Kang-Sik AU - Seo KS AD - Huen Co., Ltd., Gwanggyo Business Center 5F (#508), 156, Gwanggyo-ro, Yeongtong-gu, Suwon 16506, Korea. FAU - Son, Mi-Young AU - Son MY AUID- ORCID: 0000-0001-7590-8812 AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. AD - Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, Korea. FAU - Yoon, Joo Seog AU - Yoon JS AD - Huen Co., Ltd., Gwanggyo Business Center 5F (#508), 156, Gwanggyo-ro, Yeongtong-gu, Suwon 16506, Korea. FAU - Kim, Janghwan AU - Kim J AUID- ORCID: 0000-0003-3227-958X AD - Stem Cell Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Korea. AD - Department of Functional Genomics, KRIBB School of Bioscience, University of Science and Technology, Daejeon 34113, Korea. LA - eng GR - 2015M3A9C7030128/National Research Foundation of Korea/ GR - NRF-2018M3A9H3023077/National Research Foundation of Korea/ GR - KGS1092012/Korea Research Institute of Bioscience and Biotechnology/ PT - Journal Article DEP - 20200807 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - 0 (Leupeptins) RN - 0 (Neuroprotective Agents) RN - 0 (Phenanthrenes) RN - 5E9SXT166N (cryptotanshinone) RN - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde) SB - IM MH - Case-Control Studies MH - Cell Line MH - Cellular Reprogramming/*drug effects MH - Gene Expression Regulation/drug effects MH - Humans MH - Induced Pluripotent Stem Cells/cytology/drug effects/metabolism MH - Leupeptins/pharmacology MH - Mitochondria/metabolism MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Oxidative Stress/drug effects MH - Parkinson Disease/*drug therapy/metabolism/pathology MH - Phenanthrenes/*pharmacology PMC - PMC7463464 OTO - NOTNLM OT - Parkinson's disease OT - antioxidant OT - cryptotanshinone OT - disease modeling OT - mitochondrial dysfunction COIS- The authors declare no conflict of interest. EDAT- 2020/08/14 06:00 MHDA- 2021/03/09 06:00 PMCR- 2020/08/07 CRDT- 2020/08/14 06:00 PHST- 2020/07/21 00:00 [received] PHST- 2020/08/02 00:00 [revised] PHST- 2020/08/05 00:00 [accepted] PHST- 2020/08/14 06:00 [entrez] PHST- 2020/08/14 06:00 [pubmed] PHST- 2021/03/09 06:00 [medline] PHST- 2020/08/07 00:00 [pmc-release] AID - molecules25163602 [pii] AID - molecules-25-03602 [pii] AID - 10.3390/molecules25163602 [doi] PST - epublish SO - Molecules. 2020 Aug 7;25(16):3602. doi: 10.3390/molecules25163602.