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Molecules ; 25(16)2020 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-32784741

RESUMEN

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.


Asunto(s)
Reprogramación Celular/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Enfermedad de Parkinson/tratamiento farmacológico , Fenantrenos/farmacología , Estudios de Casos y Controles , Línea Celular , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Leupeptinas/farmacología , Mitocondrias/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología
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