Toxicity of Necrostatin-1 in Parkinson’s Disease Models
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 bee...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/6/524 |
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| author | Eva Alegre-Cortés Alicia Muriel-González Saray Canales-Cortés Elisabet Uribe-Carretero Guadalupe Martínez-Chacón Ana Aiastui Adolfo López de Munain Mireia Niso-Santano Rosa A. Gonzalez-Polo José M. Fuentes Sokhna M. S. Yakhine-Diop |
| author_facet | Eva Alegre-Cortés Alicia Muriel-González Saray Canales-Cortés Elisabet Uribe-Carretero Guadalupe Martínez-Chacón Ana Aiastui Adolfo López de Munain Mireia Niso-Santano Rosa A. Gonzalez-Polo José M. Fuentes Sokhna M. S. Yakhine-Diop |
| author_sort | Eva Alegre-Cortés |
| collection | DOAJ |
| description | 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 <i>leucine-rich repeat kinase 2</i> (<i>LRRK2)</i> 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. |
| first_indexed | 2024-03-10T19:10:11Z |
| format | Article |
| id | doaj.art-6e53fef3a6924a62ab14c3353d974cab |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T19:10:11Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6e53fef3a6924a62ab14c3353d974cab2023-11-20T03:54:13ZengMDPI AGAntioxidants2076-39212020-06-019652410.3390/antiox9060524Toxicity of Necrostatin-1 in Parkinson’s Disease ModelsEva Alegre-Cortés0Alicia Muriel-González1Saray Canales-Cortés2Elisabet Uribe-Carretero3Guadalupe Martínez-Chacón4Ana Aiastui5Adolfo López de Munain6Mireia Niso-Santano7Rosa A. Gonzalez-Polo8José M. Fuentes9Sokhna M. S. Yakhine-Diop10Department Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainCell Culture Plataform, Donostia University Hospital, 20014 San Sebastián, SpainNeuroscience Area of Biodonostia Health Research Institute, Donostia University Hospital, 20014 San Sebastián, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainDepartment Bioquímica y Biología Molecular y Genética, Facultad de Enfermería y Terapia Ocupacional, Universidad de Extremadura Avda de la Universidad s/n, 10003 Cáceres, SpainParkinson’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 <i>leucine-rich repeat kinase 2</i> (<i>LRRK2)</i> 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.https://www.mdpi.com/2076-3921/9/6/524mitochondriamitophagyMLKLnecroptosisRIProtenone |
| spellingShingle | Eva Alegre-Cortés Alicia Muriel-González Saray Canales-Cortés Elisabet Uribe-Carretero Guadalupe Martínez-Chacón Ana Aiastui Adolfo López de Munain Mireia Niso-Santano Rosa A. Gonzalez-Polo José M. Fuentes Sokhna M. S. Yakhine-Diop Toxicity of Necrostatin-1 in Parkinson’s Disease Models Antioxidants mitochondria mitophagy MLKL necroptosis RIP rotenone |
| title | Toxicity of Necrostatin-1 in Parkinson’s Disease Models |
| title_full | Toxicity of Necrostatin-1 in Parkinson’s Disease Models |
| title_fullStr | Toxicity of Necrostatin-1 in Parkinson’s Disease Models |
| title_full_unstemmed | Toxicity of Necrostatin-1 in Parkinson’s Disease Models |
| title_short | Toxicity of Necrostatin-1 in Parkinson’s Disease Models |
| title_sort | toxicity of necrostatin 1 in parkinson s disease models |
| topic | mitochondria mitophagy MLKL necroptosis RIP rotenone |
| url | https://www.mdpi.com/2076-3921/9/6/524 |
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