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Open AccessArticle

Toxicity of Necrostatin-1 in Parkinson’s Disease Models

1
Department Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, Spain
2
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28049 Madrid, Spain
3
Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), 10003 Cáceres, Spain
4
Cell Culture Plataform, Donostia University Hospital, 20014 San Sebastián, Spain
5
Neuroscience Area of Biodonostia Health Research Institute, Donostia University Hospital, 20014 San Sebastián, Spain
6
Department of Neurology, Donostia University Hospital, 20014 San Sebastian, Spain
7
Ilundain Fundazioa, 20014 San Sebastian, Spain
8
Department of Neurosciences, University of the Basque Country UPV-EHU, 20014 San Sebastián, Spain
*
Authors to whom correspondence should be addressed.
Authors contributed equally to this work.
Antioxidants 2020, 9(6), 524; https://doi.org/10.3390/antiox9060524
Received: 1 May 2020 / Revised: 10 June 2020 / Accepted: 10 June 2020 / Published: 15 June 2020
Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. This neuronal loss, inherent to age, is related to exposure to environmental toxins and/or a genetic predisposition. PD-induced cell death has been studied thoroughly, but its characterization remains elusive. To date, several types of cell death, including apoptosis, autophagy-induced cell death, and necrosis, have been implicated in PD progression. In this study, we evaluated necroptosis, which is a programmed type of necrosis, in primary fibroblasts from PD patients with and without the G2019S leucine-rich repeat kinase 2 (LRRK2) mutation and in rotenone-treated cells (SH-SY5Y and fibroblasts). The results showed that programmed necrosis was not activated in the cells of PD patients, but it was activated in cells exposed to rotenone. Necrostatin-1 (Nec-1), an inhibitor of the necroptosis pathway, prevented rotenone-induced necroptosis in PD models. However, Nec-1 affected mitochondrial morphology and failed to protect mitochondria against rotenone toxicity. Therefore, despite the inhibition of rotenone-mediated necroptosis, PD models were susceptible to the effects of both Nec-1 and rotenone. View Full-Text
Keywords: mitochondria; mitophagy; MLKL; necroptosis; RIP; rotenone mitochondria; mitophagy; MLKL; necroptosis; RIP; rotenone
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Alegre-Cortés, E.; Muriel-González, A.; Canales-Cortés, S.; Uribe-Carretero, E.; Martínez-Chacón, G.; Aiastui, A.; López de Munain, A.; Niso-Santano, M.; Gonzalez-Polo, R.A.; Fuentes, J.M.; Yakhine-Diop, S.M.S. Toxicity of Necrostatin-1 in Parkinson’s Disease Models. Antioxidants 2020, 9, 524.

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